essays about brain cancer

Brain and Spinal Cord Tumor Research Results and Study Updates

See Advances in Brain and Spinal Cord Tumor Research for an overview of recent findings and progress, plus ongoing projects supported by NCI.

FDA has granted an accelerated approval to tovorafenib (Ojemda) for kids and teens who have low-grade glioma with changes in the BRAF gene. In a small clinical trial, the drug shrank or completely eliminated tumors in nearly 70% of patients.

The activity of 34 genes can accurately predict the aggressiveness of meningiomas, a new study shows. This gene expression signature may help oncologists select the best treatments for people with this common type of brain cancer than they can with current methods.

An NCI-supported study called OPTIMUM, part of the Cancer Moonshot, was launched to improve the care of people with brain tumors called low-grade glioma in part by bringing them into glioma-related research.

Treating craniopharyngioma often requires surgery, radiation therapy, or both. But results of a study suggest that, for many, combining the targeted therapies vemurafenib (Zelboraf) and cobimetinib (Cotellic) may substantially delay, or even eliminate, the need for these treatments.

In a large clinical trial, vorasidenib slowed the growth of low-grade gliomas that had mutations in the IDH1 or IDH2 genes. Vorasidenib is the first targeted drug developed specifically to treat brain tumors.

Researchers have found that the aggressive brain cancer glioblastoma can co-opt the formation of new synapses to fuel its own growth. This neural redirection also appears to play a role in the devastating cognitive decline seen in many people with glioblastoma.

Two companion studies have found different forms of some brain tumors, diffuse midline glioma and IDH-mutant glioma, become dependent for their survival on the production of chemicals called pyrimidines. Clinical trials are planned to test a drug that blocks pyrimidine synthesis in patients with gliomas.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) shrank more brain tumors, kept the tumors at bay for longer, and caused fewer side effects than chemotherapy, trial results showed. The children all had glioma with a BRAF V600 mutation that could not be surgically removed or came back after surgery.

Two separate but complementary studies have identified a new way to classify meningioma, the most common type of brain tumor. The grouping system may help predict whether a patient’s tumor will grow back after treatment and identify new treatments.

A nanoparticle coating may help cancer drugs reach medulloblastoma tumors in the brain and make the treatment less toxic. Mice treated with nanoparticles containing palbociclib (Ibrance) and sapanisertib lived substantially longer than those treated with either drug alone.

A new test could potentially be used to identify children treated for medulloblastoma who are at high risk of their cancer returning. The test detects evidence of remaining cancer in DNA shed from medulloblastoma tumor cells into cerebrospinal fluid.

Standard radiation for medulloblastoma can cause long-term damage to a child’s developing brain. A new clinical trial suggests that the volume and dose of radiation could be safely tailored based on genetic features in the patient’s tumor.

In people with glioblastoma and other brain cancers, steroids appear to limit the effectiveness of immunotherapy drugs, a new study shows. The findings should influence how steroids are used to manage brain tumor symptoms, researchers said.

Results from two studies show that a liquid biopsy that analyzes DNA in blood accurately detected kidney cancer at early and more advanced stages and identified and classified different types of brain tumors.

A method that combines artificial intelligence with an advanced imaging technology can accurately diagnose brain tumors in fewer than 3 minutes during surgery, a new study shows. The approach can also accurately distinguish tumor from healthy tissue.

Glioblastoma cells sneak many copies of a key oncogene into circular pieces of DNA. In a new NCI-funded study, scientists found that the cells also slip several different genetic “on switches” into these DNA circles, helping to fuel the cancer’s growth.

Men and women with glioblastoma appear to respond differently to standard treatment. A new study identifies biological factors that might contribute to this sex difference.

A liquid biopsy blood test can detect DNA from brain tumors called diffuse midline gliomas, researchers have found. This minimally invasive test could be used to identify and follow molecular changes in children with these highly lethal brain tumors.

Despite continued efforts to develop new therapies for glioblastoma, none have been able to improve how long patients live appreciably. Despite some setbacks, researchers are hopeful that immunotherapy might be able to succeed where other therapies have not.

Progress against the brain cancer glioblastoma has been slow. Drs. Mark Gilbert and Terri Armstrong of NCI’s Neuro-Oncology Branch discuss why and what’s being done to change that.

Studies presented at the 2017 AACR annual meeting suggest that therapies which take advantage of the mutations in the IDH gene may be more effective than drugs that block it.

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• Published: 20 December 2019

Focusing on brain tumours and brain metastasis

Nature Reviews Cancer volume  20 ,  page 1 ( 2020 ) Cite this article

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This Focus issue highlights current research into the unique biology of brain tumours and brain metastasis and how this research might improve therapy of these often devastating diseases.

Survival for many types of malignant primary brain tumours has not improved much in the past 10 years, despite the introduction of some new treatments and despite our improved understanding of the biological bases of brain tumour development 1 , 2 . In addition, most malignant brain lesions are actually secondary brain tumours (brain metastases), and it is estimated that brain metastases will develop in up to 30% of adults who have a malignant primary tumour at another site 2 , 3 . Furthermore, brain tumours are the most common type of solid tumour in children and are the leading cause of cancer-related deaths in this population 1 , 4 . These statistics all indicate that better treatments for brain tumours and brain metastasis are a pressing need. We have therefore put together this Focus issue to highlight the diverse research in this field and the unique challenges posed by brain tumours and brain metastases.

Brain tumours are a heterogeneous group of diseases, but one important common feature is that they are subject to the unique biology of the brain and its microenvironment. The brain contains many cell types that are distinct from those found elsewhere in the body, making it challenging to extrapolate findings from cancers arising in other organs to those arising in the brain. Furthermore, the anatomy of the brain presents challenges for treating both brain tumours and brain metastases.

A prime example of both the unique biology and the anatomical challenges of treating brain tumours is the blood–brain barrier (BBB), the neurovascular unit that maintains brain homeostasis and acts as a ‘gatekeeper’, controlling the crossing of molecules and cells from the blood into the brain. Although the BBB is often disrupted in brain tumours, effective delivery of anticancer therapeutics through this blood–tumour barrier remains a challenge, as addressed by Arvanitis et al. 5 .

One aspect of the brain microenvironment that might not be as unique as initially presumed is the immune environment. The immune cell types of the brain differ from those in other organs, but, as discussed by Sampson et al. 6 , it is now becoming clear that this organ is not as ‘immune privileged’ as once thought, leading to hope that brain tumours and metastases might be successfully targeted with immunotherapies.

despite the challenges presented by brain tumours, progress is being made on many different fronts against these often devastating diseases

Gliomas account for ~80% of malignant brain tumours, and the highest grade glioma, glioblastoma, is one of the most lethal cancers in adults 3 . Interestingly, genomic sequencing efforts more than 10 years ago jump-started the field of glioma metabolism with their finding of recurrent mutations in the genes encoding the tricarboxylic acid cycle enzymes IDH1 and IDH2, but the role of metabolism in glioma pathogenesis goes beyond IDH, as discussed by Bi et al. 7 .

Medulloblastoma is one of the most common paediatric brain tumours 4 . Our understanding of this disease was advanced substantially by genomic studies reported in 2012. Since then, as discussed by Hovestadt et al. 8 , more genomic studies, as well as epigenomic, transcriptomic and proteomic profiling efforts, have provided new insights into medulloblastoma biology that will hopefully lead to improved diagnosis and therapy.

The prevalence of brain metastases in adults raises the question of what those working on primary brain tumours can learn from research on brain metastasis, and vice versa. This, and other important questions on brain metastasis, is pondered in a Viewpoint article written by four leading experts in this field 9 .

What has emerged from this collection of articles is that despite the challenges presented by brain tumours, progress is being made on many different fronts against these often devastating diseases, which will hopefully lead to improvements in survival in the next 10 years, if not sooner.

Jones, D. T. W. et al. Molecular characteristics and therapeutic vulnerabilities across paediatric solid tumours. Nat. Rev. Cancer 19 , 420–438 (2019).

Article   CAS   Google Scholar  

Lapointe, S. et al. Primary brain tumours in adults. Lancet 392 , 432–446 (2018).

Article   Google Scholar  

Weller, M. et al. Glioma. Nat. Rev. Dis. Primers 1 , 15017 (2015).

Liu, K. W. et al. Molecular mechanisms and therapeutic targets in pediatric brain tumors. Sci. Signal. 10 , eaaf7593 (2017).

Arvanitis, C. D. et al. The blood–brain barrier and blood–tumour barrier in brain tumours and metastases. Nat. Rev. Cancer https://doi.org/10.1038/s41568-019-0205-x (2019).

Article   PubMed   Google Scholar  

Sampson, J. H. et al. Brain immunology and immunotherapy in brain tumours. Nat. Rev. Cancer https://doi.org/10.1038/s41568-019-0224-7 (2019).

Bi, J. et al. Altered cellular metabolism in gliomas — an emerging landscape of actionable co-dependency targets. Nat. Rev. Cancer https://doi.org/10.1038/s41568-019-0226-5 (2019).

Hovestadt, V. et al. Medulloblastomics revisited: biological and clinical insights from thousands of patients. Nat. Rev. Cancer https://doi.org/10.1038/s41568-019-0223-8 (2019).

Boire, A. et al. Brain metastasis. Nat. Rev. Cancer https://doi.org/10.1038/s41568-019-0220-y (2019).

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New research platform assesses brain cancer mutations during surgery

Lynda De Widt

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JACKSONVILLE, Fla. — Brain cancer is difficult to treat when it starts growing, and a prevalent type, known as a glioma , has a poor five-year survival rate. In a new study published in Proceedings of the National Academy of Sciences, Mayo Clinic researchers report on a new surgical platform used during surgery that informs critical decision-making about tumor treatment within minutes. Time is of the utmost importance when dealing with aggressive malignant tumors.

The platform uses mass spectrometry to identify a key gene mutation in brain cancer, known as isocitrate dehydrogenase (IDH) mutations, in real time. Mass spectrometry is a sensitive technique used to analyze substances in tissue samples, including those altered in cancer.

The study involved more than 240 small tissue biopsies from patients undergoing asleep and awake brain surgery for suspected glioma at Mayo Clinic between 2021 and 2023, and an additional 137 biopsies from an international collaborator. Neurosurgeons collected biopsy samples from the core of the tumor to identify the mutations, as well as from areas around it, to assess if the tumor had spread.

Each tissue sample was placed on a glass slide steps away from the patients during ongoing surgery. The samples were analyzed through the mass spectrometer, which allowed researchers to rapidly assess — within two minutes — whether an IDH mutation was present.

The researchers say that, in addition to enabling real-time diagnosis, the platform allows surgeons to determine a patient's prognosis and perform tumor resection to improve patient outcomes. In the future, the new platform will help surgeons take advantage of the window of opportunity in the operating room to tailor treatment to the molecular features of a tumor, a more personalized approach to medicine.

Researchers hope new therapies developed to target IDH mutations can be delivered in the operating room at the time of surgery.

"The ability to identify this mutation during brain surgery means that one day in the future we may be able to treat patients with this specific mutation locally before they leave the operating room," says the study's senior author, Alfredo Quiñones-Hinojosa, M.D. , dean of research and chair of the Department of Neurosurgery at Mayo Clinic in Florida.

"Therefore, we will be able to bring the fight against cancer to the operating room, before chemotherapy and radiation treatments begin, and before the disease has progressed and invaded further." Dr. Quiñones-Hinojosa is also director of the Brain Tumor Stem Cell Research Laboratory .

In the study, researchers were able to diagnose IDH gene mutations with 100% accuracy. They are conducting more research to find other signatures in tumors where the mutation is absent. In addition, they plan to broaden their discoveries to include other types of brain cancers.

This study was supported in part by the National Cancer Institute of the National Institutes of Health under award number R33CA240181. For a full list of authors, funding and disclosures, see the paper .

About Mayo Clinic Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the  Mayo Clinic News Network  for additional Mayo Clinic news.

Media contact:

• Kelley Luckstein, Mayo Clinic Communications, [email protected]
• Mayo Clinic Minute: No ‘lesser evil’ when it comes to tobacco use A Mayo Clinic virologist explains FLiRT and why you may need a new COVID-19 vaccination 

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Ancient Skull With Brain Cancer Preserves Clues to Egyptian Medicine

Cuts in the cranium, which is more than 4,000 years old, hint that people in the ancient civilization attempted to treat a scourge that persists today.

By Jordan Pearson

Fluctuating disease rates , innovative treatments and talk of “moonshots” in the White House may make cancer seem like a modern scourge. But a new discovery highlights how humans dealt with the illness and hunted for cures as far back as the time of the ancient Egyptians.

Scientists led by Edgard Camarós , a paleopathologist at the University of Santiago de Compostela in Spain, were studying an approximately 4,600-year-old Egyptian skull when they found signs of brain cancer and its treatment.

“There was an uncomfortable silence in the room, because we knew what we had just discovered,” Dr. Camarós said.

Using a microscope, he and Tatiana Tondini of the University of Tübingen in Germany and Albert Isidro of the University Hospital Sagrat Cor in Spain, the study’s other authors, found cut marks around the skull’s edges surrounding dozens of lesions that earlier researchers had linked to metastasized brain cancer. The shape of the cuts indicated that they had been made with a metal tool. This discovery, reported in a study published Wednesday in the journal Frontiers in Medicine , suggests that ancient Egyptians studied brain cancer using surgery. If the cuts were made while the person was alive, they may have even attempted to treat it.

The new discovery not only expands scientific knowledge of Egyptian medicine, it may also push back the timeline of humanity’s documented attempts to treat cancer by up to 1,000 years.

Cancer has bedeviled humans for as long as we have existed, and it even afflicted life on Earth long before .

“Cancer is as old as time,” Dr. Camarós said. “Even dinosaurs suffered from cancer.”

Paleopathologists like Dr. Camarós study the evolution of a disease as well as attempts to understand or treat it. For example, we know that humans in prehistory were afflicted with cancers that no longer exist. He and his colleagues hope that unraveling cancer’s shifting nature over millenniums may reveal information that can help design treatments for today.

While cancer was probably not well understood, medicine in Egypt was advanced compared with much of the ancient world. An Egyptian document called the Edwin Smith Papyrus , which was written roughly 3,600 years ago, refers to what some researchers believe is a cancer case. That text describes “a grave disease” for which there “was no treatment.”

People in ancient Egypt also operated on skulls in other ways. Dr. Camarós’s team also reports in the study that they found evidence of successful treatment for a traumatic injury on another cranium, this one 2,600 years old.

Casey L. Kirkpatrick, a bioarchaeologist and a postdoctoral researcher at the Max Planck Institute for Evolutionary Anthropology in Germany, said the new paper presents the first physical evidence of possible cancer treatment by ancient Egyptians.

And by documenting additional ancient historical evidence of the disease, Dr. Kirkpatrick said the study had another benefit.

“It can also remind us that cancer is not a modern disease,” she said, “which might help to relieve some guilt in those currently affected by cancer who are concerned about the role that their lifestyle played in its development.”

Just as cancer treatment was a frontier for ancient Egyptians, exploration of the deep past by modern researchers is fraught with uncertainty. The researchers say it is impossible to determine whether the skull’s surgical markings were made before death — suggesting treatment — or after. Many cancers also arise in soft tissues, leaving bones unaffected. This presents a challenge for modern scientists because bones are all that typically survive in the fossil record.

Despite these obstacles, Dr. Camarós said the new discovery gave scientists a fresh perspective on what to look for. He plans to search for similar evidence in ancient sites in Kenya next.

“I’m sure this is just one example,” he said.

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New glioblastoma treatment reaches human brain tumor and helps immune cells recognize cancer cells

by Northwestern University

In a major advance for the treatment of the deadly brain cancer glioblastoma, Northwestern Medicine scientists have used ultrasound technology to penetrate the blood-brain barrier and provide a small dose of a chemotherapy and immunotherapy drug cocktail. The study found that this treatment boosted the immune system's recognition of the cancer cells and could lead to a new treatment approach.

The scientists made several breakthroughs reported in a new study published in Nature Communications .

Scientists showed for the first time that a skull-implantable ultrasound device can enhance the penetration of the chemotherapy drug doxorubicin and immune checkpoint blockade antibodies—a novel immunotherapy treatment combination—into the human brain. The device produces microbubbles that temporarily open the blood-brain barrier , allowing the immunotherapy to enter the brain.

The scientists also showed for the first time that a small dose of doxorubicin (smaller than the dose used for traditional chemotherapy regimens) delivered with the immune checkpoint antibodies can boost the recognition of malignant glioblastoma cells by the immune system and reinvigorate the lymphocytes ( immune cells ) that are in charge of attacking the cancer cells .

An immune checkpoint blockade antibody blocks the deactivation of the immune system by the cancer cells. The immune system has built-in brakes—called immune checkpoints—so that it doesn't overdo it and injure the body when attacking cancer and infections. Glioblastoma evolves to activate the brakes, and therefore, the immune system (i.e., lymphocytes) won't attack it.

In addition to the tumor cells , glioblastoma contains other cell populations called macrophages and microglia. These are the most abundant components of the tumor microenvironment and the cells that glioblastoma modulates to inhibit lymphocytes. The study showed that the chemo and antibody cocktail altered these cells, enabling the lymphocytes to recognize and kill the cancer cells.

"This is the first report in humans where an ultrasound device has been used to deliver drugs and antibodies to glioblastoma to change the immune system, so it can recognize and attack the brain cancer," said co-corresponding author Dr. Adam Sonabend, associate professor of neurological surgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine neurosurgeon. "This could be a major advance for the treatment of glioblastoma, which has been a frustratingly difficult cancer to treat, in part due to poor penetration of circulating drugs and antibodies into the brain."

The study was conducted on four patients who had advanced progression of their tumors. They had already been treated with conventional chemotherapy for their tumors as well as an experimental treatment in a clinical trial, but both times, the tumors returned.

"This is a great example of translational bench-to-bedside-back-to-bench research, which sets an exceptional scenario to learn about the ability of the immune system to kill brain tumors in real-time upon treatment," said co-corresponding author Catalina Lee-Chang, assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine. "Given the lack of effective immune response against these deadly tumors, these findings encourage us to envision a potential new treatment approach."

Clinical trial launched with new treatment

These new findings are the basis for a novel clinical trial that was just launched at Northwestern using ultrasound to deliver immunotherapy for glioblastoma. The trial will initially enroll 10 participants to determine the safety of the treatment, followed by 15 additional to measure whether the treatment can prolong survival.

Previous large clinical trials have failed to show that this type of immunotherapy can prolong survival in glioblastoma patients. Sonabend, however, believes that by enhancing the delivery of these antibodies and drugs into the brain and relying on biomarkers that indicate which tumors are most susceptible to immunotherapy, this treatment might be shown to be effective for some glioblastoma patients.

"Here we show in a small cohort of patients that when you use this technology, you can enhance the delivery of the chemotherapy and the antibodies, and change the tumor's microenvironment, so the immune system can recognize the tumor," Sonabend said.

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Diet and Nutrition for Brain Tumor Patients

A brain tumor diagnosis can be overwhelming, but maintaining a nutritious diet is an empowering step you can take to manage your well-being. Eating well fuels your body during treatment enhances your quality of life, and can even impact treatment outcomes. 

This guide provides practical tips for creating a balanced, nourishing diet specifically tailored to brain tumor patients. We'll explore the importance of key nutrients and healthy eating habits to empower you to recover.

The Role of Diet in Brain Tumor Treatment

Diet plays a crucial role in brain tumor management . A well-balanced plan strengthens your immune system, speeds healing, and minimizes side effects from treatments like chemotherapy and radiation. Proper nutrition provides the building blocks your body needs to repair tissues and maintain vital functions. 

Maintaining optimal nutrition is even more important for brain tumor patients. Treatments can be quite demanding, leading to fatigue and potential nutritional deficiencies. Eating various nutrient-rich foods can combat fatigue, support cognitive function, and improve overall health. 

Also, specific dietary strategies can help manage common side effects like nausea, appetite loss, and taste changes. Consulting with a registered dietitian (RD) or healthcare professional can provide personalized dietary plans to make sure you get the nutrients needed to support your journey.

Essential Nutrients for Brain Tumor Patients

A balanced and nutrient-rich diet is crucial for brain tumor patients to support their treatment and recovery process. Understanding the role of specific nutrients can help plan meals that align with the unique needs of brain tumor treatment. Here are some essential nutrients that brain tumor patients should focus on:

Proteins: Building Blocks for Recovery

• Role : Protein is essential for the body's repair and regeneration processes. It helps rebuild tissues, maintain muscle mass, and support immune function.
• Sources : Include lean meats, poultry, fish, eggs, dairy products, legumes, nuts, and seeds in your diet. Plant-based protein sources like beans, lentils, and tofu are also excellent options.

Healthy Fats: Supporting Brain Health

• Role : Healthy fats are important for brain function and overall health. They help reduce inflammation and provide energy.
• Sources : Incorporate fatty fish like salmon, mackerel, and sardines, as well as flaxseeds, chia seeds, walnuts, and algae-based supplements. Other healthy fat sources include avocados, olive oil, and nuts.

Carbohydrates: Fuel for Energy

• Role : Carbohydrates are the body's primary energy source. Complex carbohydrates provide sustained energy and are rich in fiber, which aids digestion.
• Sources : Choose whole grains like brown rice, quinoa, oats, and whole wheat products. Include a variety of fruits, vegetables, and legumes to ensure a steady intake of vitamins and minerals.

Vitamins and Minerals: Boosting Immunity and Strength

Key Vitamins for Brain Tumor Patients : Vitamins A, C, and E, along with B vitamins, play significant roles in supporting the immune system and promoting overall health.

Sources of Essential Vitamins :

• Vitamin A : Found in carrots, sweet potatoes, and leafy greens.
• Vitamin C : Present in citrus fruits, berries, bell peppers, and broccoli.
• Vitamin E : Available in nuts, seeds, and green leafy vegetables.
• B Vitamins : Found in whole grains, dairy products, meats, and leafy greens.

Key Minerals for Brain Tumor Patients : Zinc, selenium, and magnesium are important for immune function, healing, and maintaining energy levels.

Sources of Essential Minerals :

• Zinc : Found in meat, shellfish, legumes, seeds, and nuts.
• Selenium : Present in Brazil nuts, seafood, and eggs.
• Magnesium : Found in dark chocolate, avocados, nuts, seeds, and whole grains.

Brain tumor patients can support their body's needs during treatment and recovery by incorporating these essential nutrients into their diet. If you’re still unsure where to start, chat with a healthcare professional or nutritionist to develop a personalized nutrition plan.

Special Diets for Brain Tumor Patients

Different dietary approaches can help brain tumor patients manage symptoms and improve overall health. Here are some special diets that may be beneficial:

The Ketogenic Diet

• The ketogenic diet is a high-fat, low-carbohydrate diet that forces the body to burn fats rather than carbohydrates for energy. This diet can help reduce inflammation and provide a steady energy source for the brain.

Potential Benefits:

• May help reduce the growth of tumor cells.
• Can provide an alternative energy source for brain cells.
• May improve cognitive function and reduce treatment-related fatigue.

How To Start:

• Focus on high-fat foods such as avocados, nuts, seeds, and oils.
• Include moderate amounts of protein from sources like meat, fish, and eggs.
• Limit carbohydrate intake by avoiding grains, starchy vegetables, and sugary foods.

Plant-Based Diet

• A plant-based diet emphasizes whole foods derived from plants, which can be rich in antioxidants, vitamins, and minerals.
• Can help reduce inflammation and support overall health.

How To Start: :

• Focus on fruits, vegetables, whole grains, legumes, nuts, and seeds.
• Limit or avoid animal products such as meat, dairy, and eggs.
• Get adequate protein intake through legumes, tofu, tempeh, and other plant-based protein sources.

Anti-Inflammatory Diet

Role of Anti-Inflammatory Foods:

• An anti-inflammatory diet can help manage inflammation, which is often associated with cancer and its treatment.

Key Foods to Include:

• Fruits and vegetables, especially berries, leafy greens, and cruciferous vegetables.
• Fatty fish like salmon and mackerel, are rich in omega-3 fatty acids.
• Nuts, seeds, and olive oil.
• Spices such as turmeric and ginger.

Foods to Avoid

Certain foods can worsen symptoms or interfere with treatment. Here are some foods that brain tumor patients should limit or avoid:

Processed Foods

Negative Impacts:

• Processed foods often contain unhealthy fats, excessive sugars, and artificial additives that can contribute to inflammation and other health issues.

Examples to Avoid:

• Packaged snacks, fast food, processed meats, and sugary cereals.

Sugary Foods and Drinks

Effects of Sugar:

• High sugar intake can lead to weight gain, increased inflammation, and a weakened immune system.

Healthier Alternatives:

• Opt for natural sweeteners like honey or maple syrup in moderation.
• Choose whole fruits instead of sugary snacks and desserts.

High-Sodium Foods

Risks of High Sodium Intake:

• Excessive sodium can lead to high blood pressure and increased fluid retention, which can be problematic for brain tumor patients.

Tips for Reducing Sodium:

• Avoid canned soups, processed snacks, and fast food.
• Use herbs and spices to flavor food instead of salt.

Foods to Eat After Brain Surgery

After brain surgery, it's important to focus on a diet that supports healing and recovery. Patients should aim for a balanced diet of essential nutrients to help the body repair tissues and maintain strength. Here are some recommended foods:

• Lean Proteins : Essential for tissue repair and muscle maintenance. Include chicken, turkey, fish, eggs, tofu, and legumes.
• Healthy Fats : Support brain health and reduce inflammation. Incorporate avocados, nuts, seeds, olive oil, and fatty fish like salmon.
• Whole Grains : Provide sustained energy and are rich in fiber. Opt for brown rice, quinoa, whole wheat bread, and oats.
• Fruits and Vegetables : Packed with vitamins, minerals, and antioxidants. Focus on a variety of colorful fruits and vegetables to ensure a broad spectrum of nutrients.
• Hydration : Staying well-hydrated is crucial. Drink plenty of water and include hydrating foods such as cucumbers, oranges, and watermelon.

Support and Resources  

Duke University's Tisch Brain Tumor Center is dedicated to providing comprehensive care for brain tumor patients, addressing both their medical and nutritional needs. Here’s how Duke can assist:

Comprehensive Nutrition Counseling

• Personalized Nutrition Plans : Duke's dietitians and nutritionists develop tailored nutrition plans for brain tumor patients, focusing on optimizing nutrient intake, managing treatment side effects, and supporting overall health. These personalized plans consider individual dietary preferences and treatment regimens to ensure the best possible outcomes.
• Ongoing Support and Education : Patients receive continuous support and education on maintaining a balanced diet during and after treatment. This includes practical tips for meal planning, grocery shopping, and preparing nutrient-dense meals. Duke also offers resources like cooking classes and workshops to help patients integrate healthy eating habits into their daily routines.

Research and Innovation

• Cutting-Edge Research : As a leading research institution, Duke uses cutting-edge research to understand the impact of diet and nutrition on brain tumor treatment outcomes. Patients benefit from access to the latest findings and evidence-based recommendations that can enhance their care.
• Clinical Trials : Duke conducts clinical trials exploring various aspects of brain tumor treatment, including dietary interventions. Participating in these trials can provide patients with opportunities to access new therapies and nutritional strategies that are not yet widely available.

Patient-Centered Care

• Holistic Support : Duke’s holistic approach addresses emotional, psychological, and social needs. Clinical social workers and neuropsychologists provide counseling and support to help patients and their families cope with the challenges of a brain tumor diagnosis and treatment.
• Patient and Family Resources : Duke offers extensive resources for patients and their families, including educational materials, support groups, and one-on-one counseling. These resources help patients navigate their treatment journey with confidence and ease.

Discover the Best Clinic For Brain Tumor Testing

If you’re considering undergoing treatment for a brain tumor, visit our website to learn more about our vision. Duke University’s Tisch Brain Tumor Center offers hope and empowers anyone diagnosed with brain tumors. 

If you are considering treatment for brain cancer , visit our website to request an appointment with one of our leading physicians.                                       

Interested in joining the team of world-leading Neuro-Oncology doctors and practitioners? Visit our education & training page to learn more. You can also support the clinic by donating funds directly to patient care, research, education, and treatment for brain tumors.  

Related readings:

• How Do You Get a Brain Tumor?    
• How Long Can You Have a Brain Tumor Without Knowing?

Frequently Asked Questions About Brain Tumor Nutrition

What should brain tumor patients avoid?

Brain tumor patients should avoid:

• Processed Foods : These often contain unhealthy fats, excessive sugars, and artificial additives that can contribute to inflammation and other health issues.
• Sugary Foods and Drinks : High sugar intake can lead to weight gain, increased inflammation, and a weakened immune system.
• High-Sodium Foods : Excessive sodium can lead to high blood pressure and increased fluid retention, which can be problematic for brain tumor patients.
• Alcohol and Caffeine : These can contribute to dehydration and may interact negatively with certain medications​.

What is the best food for brain tumor patients?

Brain tumor patients should focus on a diet rich in:

• Proteins : Lean meats, poultry, fish, eggs, dairy products, legumes, nuts, and seeds.
• Healthy Fats : Avocados, nuts, seeds, olive oil, and fatty fish like salmon and mackerel, which are high in omega-3 fatty acids.
• Complex Carbohydrates : Whole grains such as brown rice, quinoa, oats, and whole wheat products.
• Fruits and Vegetables : A variety of fresh, frozen, or canned (without added sugars or salt) fruits and vegetables to ensure a steady intake of vitamins and minerals​.

Has anyone ever beat stage 4 brain cancer?

While stage 4 brain cancer, such as glioblastoma , is extremely aggressive and challenging to treat, there have been cases where patients have experienced long-term survival and remission. Advances in treatments, including surgery, radiation, chemotherapy, and immunotherapy, have improved outcomes for some patients. Each patient's prognosis depends on various factors, including the tumor's location, size, genetic mutations, and the patient's overall health.

What exercises are good for brain tumor patients?

Engaging in regular physical activity can help improve the strength, flexibility, and overall well-being of brain tumor patients. Recommended exercises include:

• Walking : A low-impact exercise that can help improve cardiovascular health and stamina.
• Yoga and Stretching : These activities can enhance flexibility, reduce stress, and improve balance.
• Strength Training : Using light weights or resistance bands can help maintain muscle mass and strength.
• Swimming : A gentle, full-body workout that is easy on the joints and can help improve endurance.
• Balance Exercises : Activities like tai chi can help improve coordination and reduce the risk of falls.

Patients should always consult with their healthcare team before starting any new exercise regimen to ensure it is safe and appropriate for their specific condition. For more information on diet, nutrition, and overall care for brain tumor patients, visit the Duke University Tisch Brain Tumor Center .

Brain tumor

A brain tumor is a growth of cells in the brain or near it. Brain tumors can happen in the brain tissue. Brain tumors also can happen near the brain tissue. Nearby locations include nerves, the pituitary gland, the pineal gland, and the membranes that cover the surface of the brain.

Brain tumors can begin in the brain. These are called primary brain tumors. Sometimes, cancer spreads to the brain from other parts of the body. These tumors are secondary brain tumors, also called metastatic brain tumors.

Many different types of primary brain tumors exist. Some brain tumors aren't cancerous. These are called noncancerous brain tumors or benign brain tumors. Noncancerous brain tumors may grow over time and press on the brain tissue. Other brain tumors are brain cancers, also called malignant brain tumors. Brain cancers may grow quickly. The cancer cells can invade and destroy the brain tissue.

Brain tumors range in size from very small to very large. Some brain tumors are found when they are very small because they cause symptoms that you notice right away. Other brain tumors grow very large before they're found. Some parts of the brain are less active than others. If a brain tumor starts in a part of the brain that's less active, it might not cause symptoms right away. The brain tumor size could become quite large before the tumor is detected.

Brain tumor treatment options depend on the type of brain tumor you have, as well as its size and location. Common treatments include surgery and radiation therapy.

There are many types of brain tumors. The type of brain tumor is based on the kind of cells that make up the tumor. Special lab tests on the tumor cells can give information about the cells. Your health care team uses this information to figure out the type of brain tumor.

Some types of brain tumors usually aren't cancerous. These are called noncancerous brain tumors or benign brain tumors. Some types of brain tumors usually are cancerous. These types are called brain cancers or malignant brain tumors. Some brain tumor types can be benign or malignant.

Benign brain tumors tend to be slow-growing brain tumors. Malignant brain tumors tend to be fast-growing brain tumors.

Types of brain tumors include:

• Gliomas and related brain tumors. Gliomas are growths of cells that look like glial cells. The glial cells surround and support nerve cells in the brain tissue. Types of gliomas and related brain tumors include astrocytoma , glioblastoma , oligodendroglioma and ependymoma . Gliomas can be benign, but most are malignant. Glioblastoma is the most common type of malignant brain tumor.
• Choroid plexus tumors. Choroid plexus tumors start in cells that make the fluid that surrounds the brain and spinal cord. This fluid is called cerebrospinal fluid. Choroid plexus tumors are located in the fluid-filled cavities in the brain, called the ventricles. Choroid plexus tumors can be benign or malignant. Choroid plexus carcinoma is the malignant form of this type of brain tumor. It's more common in children.
• Embryonal tumors. Embryonal tumors begin in cells that are left over from fetal development. The cells, called embryonal cells, stay in the brain after birth. Embryonal tumors are malignant brain tumors that happen most often in babies and young children. The most common type of embryonal tumor is medulloblastoma . It's usually located in the lower back part of the brain, called the cerebellum.
• Germ cell tumors. Germ cell tumors start in reproductive cells, called germ cells, that go on to become the sperm and egg cells. Germ cells are mostly in the ovaries and testicles. But sometimes they're in other parts of the body, including the brain. When germ cell tumors happen in the brain, they're often located near the pineal gland or the pituitary gland. Germ cell tumors are mostly benign. They're more common in children.
• Pineal tumors. Pineal tumors start in and around the brain's pineal gland. The pineal gland is located in the center of the brain. It makes a hormone called melatonin that helps with sleep. Pineal tumors can be benign or malignant. Pineoblastoma is a malignant type of pineal tumor that's most common in children.
• Meningiomas. Meningiomas are brain tumors that start in the membranes around the brain and spinal cord. Meningiomas are usually benign, but sometimes they can be malignant. Meningiomas are the most common type of benign brain tumor.
• Nerve tumors. Nerve tumors are growths that happen in and around nerves. The most common type that happens in the head is acoustic neuroma , also called schwannoma. This benign tumor is located on the main nerve that connects the inner ear to the brain.
• Pituitary tumors. Brain tumors can begin in and around the pituitary gland. This small gland is located near the base of the brain. Most tumors that happen in and around the pituitary gland are benign. Pituitary tumors happen in the pituitary gland itself. Craniopharyngioma is a type of brain tumor that happens near the pituitary gland.
• Other brain tumors. Many other types of rare tumors can happen in and around the brain. Tumors can start in the muscles, blood vessels and connective tissue around the brain. Tumors can form in the bones of the skull. Malignant brain tumors can start from the germ-fighting immune system cells in the brain. This type of brain cancer is called primary central nervous system lymphoma.

The signs and symptoms of a brain tumor depend on the brain tumor's size and location. Symptoms also might depend on how fast the brain tumor is growing, which is also called the tumor grade.

General signs and symptoms caused by brain tumors may include:

• Headache or pressure in the head that is worse in the morning.
• Headaches that happen more often and seem more severe.
• Headaches that are sometimes described as tension headaches or migraines.
• Nausea or vomiting.
• Eye problems, such as blurry vision, seeing double or losing sight on the sides of your vision.
• Losing feeling or movement in an arm or a leg.
• Trouble with balance.
• Speech problems.
• Feeling very tired.
• Confusion in everyday matters.
• Memory problems.
• Having trouble following simple commands.
• Personality or behavior changes.
• Seizures, especially if there is no history of seizures.
• Hearing problems.
• Dizziness or a sense that the world is spinning, also called vertigo.
• Feeling very hungry and gaining weight.

Brain tumors that aren't cancerous tend to cause symptoms that develop slowly. Noncancerous brain tumors also are called benign brain tumors. They might cause subtle symptoms that you don't notice at first. The symptoms might get worse over months or years.

Cancerous brain tumors cause symptoms that get worse quickly. Cancerous brain tumors also are called brain cancers or malignant brain tumors. They cause symptoms that come on suddenly. They get worse in a matter of days or weeks.

Brain tumor headaches

Headaches are the most common symptom of brain tumors. Headaches happen in about half of people with brain tumors. Headaches can happen if a growing brain tumor presses on healthy cells around it. Or a brain tumor can cause swelling in the brain that increases pressure in the head and leads to a headache.

Headache pain caused by brain tumors is often worse when you wake up in the morning. But it can happen at any time. Some people have headaches that wake them from sleep. Brain tumor headaches tend to cause pain that's worse when coughing or straining. People with brain tumors most often report that the headache feels like a tension headache. Some people say the headache feels like a migraine.

Brain tumors in the back of the head might cause a headache with neck pain. If the brain tumor happens in the front of the head, the headache might feel like eye pain or sinus pain.

Brain tumor symptoms by location

The main part of the brain is called the cerebrum. Brain tumors in different parts of the cerebrum might cause different symptoms.

• Brain tumors in the front of the brain. The frontal lobes are in the front of the brain. They control thinking and movement. Frontal lobe brain tumors might cause balance problems and trouble walking. There might be personality changes, such as forgetfulness and lack of interest in usual activities. Sometimes family members notice that the person with the brain tumor seems different.
• Brain tumors in the middle of the brain. The parietal lobes are in the upper middle part of the brain. They help process information about touch, taste, smell, vision and hearing. Parietal lobe brain tumors can cause problems related to the senses. Examples include vision problems and hearing problems.
• Brain tumors in the back of the brain. The occipital lobes are in the back of the brain. They control vision. Occipital lobe brain tumors can cause vision loss.
• Brain tumors in the lower part of the brain. The temporal lobes are on the sides of the brain. They process memories and senses. Temporal lobe brain tumors can cause memory problems. They might cause someone to see, taste or smell something that isn't there. Sometimes the taste or smell is unpleasant or unusual.

When to see a doctor

Make an appointment with your health care provider if you have persistent signs and symptoms that worry you.

Brain tumors that begin in the brain

Brain tumors that start as a growth of cells in the brain are called primary brain tumors. They might start right in the brain or in the tissue nearby. Nearby tissue might include the membranes that cover the brain, called meninges. Brain tumors also can happen in nerves, the pituitary gland and the pineal gland.

Brain tumors happen when cells in or near the brain get changes in their DNA. A cell's DNA holds the instructions that tell the cell what to do. The changes tell the cells to grow quickly and continue living when healthy cells would die as part of their natural life cycle. This makes a lot of extra cells in the brain. The cells can form a growth called a tumor.

It's not clear what causes the DNA changes that lead to brain tumors. For many people with brain tumors, the cause is never known. Sometimes parents pass DNA changes to their children. The changes can increase the risk of having a brain tumor. These hereditary brain tumors are rare. If you have a family history of brain tumors, talk about it with your health care provider. You might consider meeting with a health care provider trained in genetics to understand whether your family history increases your risk of having a brain tumor.

When brain tumors happen in children, they're likely to be primary brain tumors. In adults, brain tumors are more likely to be cancer that started somewhere else and spread to the brain.

Cancer that spreads to the brain

Secondary brain tumors happen when cancer starts somewhere else and spreads to the brain. When cancer spreads, it's called metastatic cancer.

Any cancer can spread to the brain, but common types include:

• Breast cancer.
• Colon cancer.
• Kidney cancer.
• Lung cancer.

It's not clear why some cancers spread to the brain and others are more likely to spread to other places.

Secondary brain tumors most often happen in people who have a history of cancer. Rarely, a brain tumor may be the first sign of cancer that began somewhere else in the body.

In adults, secondary brain tumors are far more common than are primary brain tumors.

Risk factors

In most people with primary brain tumors, the cause isn't clear. But doctors have identified some factors that may raise the risk.

Risk factors include:

• Age. Brain tumors can happen at any age, but they happen most often in older adults. Some brain tumors mostly affect adults. Some brain tumors happen most often in children.
• Race. Anyone can get a brain tumor. But some types of brain tumors are more common in people of certain races. For example, gliomas are more common in white people. Meningiomas are more common in Black people.

Exposure to radiation. People who have been exposed to a strong type of radiation have an increased risk of brain tumor. This strong radiation is called ionizing radiation. The radiation is strong enough to cause DNA changes in the body's cells. The DNA changes can lead to tumors and cancers. Examples of ionizing radiation include radiation therapy used to treat cancer and radiation exposure caused by atomic bombs.

Low-level radiation from everyday objects isn't linked to brain tumors. Low levels of radiation include the energy that comes from cellphones and radio waves. There is no convincing evidence that using cellphones causes brain tumors. But more studies are happening to make sure.

• Inherited syndromes that increase the risk of brain tumor. Some DNA changes that increase the risk of brain tumor run in families. Examples include the DNA changes that cause neurofibromatosis 1 and 2, tuberous sclerosis, Lynch syndrome, Li-Fraumeni syndrome, Von Hippel-Lindau disease, familial adenomatous polyposis, Cowden syndrome, and Gorlin syndrome.

There's no way to prevent brain tumors. If you get a brain tumor, you didn't do anything to cause it.

People with an increased risk of brain tumor might consider screening tests. Screening isn't brain tumor prevention. But screening might help find a brain tumor when it's small and treatment is more likely to be successful.

If you have a family history of brain tumor or inherited syndromes that increase the risk of brain tumor, talk about it with your health care provider. You might consider meeting with a genetic counselor or other health care provider trained in genetics. This person can help you understand your risk and ways to manage it. For example, you might consider brain tumor screening tests. Testing might include an imaging test or a neurological exam to test your vision, hearing, balance, coordination and reflexes.

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• Cancer Control
• v.28; Jan-Dec 2021

Cancer Biology, Epidemiology, and Treatment in the 21st Century: Current Status and Future Challenges From a Biomedical Perspective

Patricia piña-sánchez.

1 Oncology Research Unit, Oncology Hospital, Mexican Institute of Social Security, Mexico

Antonieta Chávez-González

Martha ruiz-tachiquín, eduardo vadillo, alberto monroy-garcía, juan josé montesinos, rocío grajales.

2 Department of Medical Oncology, Oncology Hospital, Mexican Institute of Social Security, Mexico

Marcos Gutiérrez de la Barrera

3 Clinical Research Division, Oncology Hospital, Mexican Institute of Social Security, Mexico

Hector Mayani

Since the second half of the 20th century, our knowledge about the biology of cancer has made extraordinary progress. Today, we understand cancer at the genomic and epigenomic levels, and we have identified the cell that starts neoplastic transformation and characterized the mechanisms for the invasion of other tissues. This knowledge has allowed novel drugs to be designed that act on specific molecular targets, the immune system to be trained and manipulated to increase its efficiency, and ever more effective therapeutic strategies to be developed. Nevertheless, we are still far from winning the war against cancer, and thus biomedical research in oncology must continue to be a global priority. Likewise, there is a need to reduce unequal access to medical services and improve prevention programs, especially in countries with a low human development index.

Introduction

During the last one hundred years, our understanding of the biology of cancer increased in an extraordinary way. 1 - 4 Such a progress has been particularly prompted during the last few decades because of technological and conceptual progress in a variety of fields, including massive next-generation sequencing, inclusion of “omic” sciences, high-resolution microscopy, molecular immunology, flow cytometry, analysis and sequencing of individual cells, new cell culture techniques, and the development of animal models, among others. Nevertheless, there are many questions yet to be answered and many problems to be solved regarding this disease. As a consequence, oncological research must be considered imperative.

Currently, cancer is one of the illnesses that causes more deaths worldwide. 5 According to data reported in 2020 by the World Health Organization (WHO), cancer is the second cause of death throughout the world, with 10 million deaths. 6 Clearly, cancer is still a leading problem worldwide. With this in mind, the objective of this article is to present a multidisciplinary and comprehensive overview of the disease. We will begin by analyzing cancer as a process, focusing on the current state of our knowledge on 4 specific aspects of its biology. Then, we will look at cancer as a global health problem, considering some epidemiological aspects, and discussing treatment, with a special focus on novel therapies. Finally, we present our vision on some of the challenges and perspectives of cancer in the 21 st century.

The Biology of Cancer

Cancer is a disease that begins with genetic and epigenetic alterations occurring in specific cells, some of which can spread and migrate to other tissues. 4 Although the biological processes affected in carcinogenesis and the evolution of neoplasms are many and widely different, we will focus on 4 aspects that are particularly relevant in tumor biology: genomic and epigenomic alterations that lead to cell transformation, the cells where these changes occur, and the processes of invasion and metastasis that, to an important degree, determine tumor aggressiveness.

Cancer Genomics

The genomics of cancer can be defined as the study of the complete sequence of DNA and its expression in tumor cells. Evidently, this study only becomes meaningful when compared to normal cells. The sequencing of the human genome, completed in 2003, was not only groundbreaking with respect to the knowledge of our gene pool, but also changed the way we study cancer. In the post-genomic era, various worldwide endeavors, such as the Human Cancer Genome Project , the Cancer Genome ATLAS (TCGA), the International Cancer Genome Consortium, and the Pan-Cancer Analysis Working Group (PCAWG), have contributed to the characterization of thousands of primary tumors from different neoplasias, generating more than 2.5 petabytes (10 15 ) of genomic, epigenomic, and proteomic information. This has led to the building of databases and analytical tools that are available for the study of cancer from an “omic” perspective, 7 , 8 and it has helped to modify classification and treatment of various neoplasms.

Studies in the past decade, including the work by the PCAWG, have shown that cancer generally begins with a small number of driving mutations (4 or 5 mutations) in particular genes, including oncogenes and tumor-suppressor genes. Mutations in TP53, a tumor-suppressor gene, for example, are found in more than half of all cancer types as an early event, and they are a hallmark of precancerous lesions. 9 - 12 From that point on, the evolution of tumors may take decades, throughout which the mutational spectrum of tumor cells changes significantly. Mutational analysis of more than 19 000 exomes revealed a collection of genomic signatures, some associated with defects in the mechanism of DNA repair. These studies also revealed the importance of alterations in non-coding regions of DNA. Thus, for example, it has been observed that various pathways of cell proliferation and chromatin remodeling are altered by mutations in coding regions, while pathways, such as WNT and NOTCH, can be disrupted by coding and non-coding mutations. To the present date, 19 955 genes that codify for proteins and 25 511 genes for non-coding RNAs have been identified ( https://www.gencodegenes.org/human/stats.html ). Based on this genomic catalogue, the COSMIC (Catalogue Of Somatic Mutations In Cancer) repository, the most robust database to date, has registered 37 288 077 coding mutations, 19 396 fusions, 1 207 190 copy number variants, and 15 642 672 non-coding variants reported up to August 2020 (v92) ( https://cosmic-blog.sanger.ac.uk/cosmic-release-v92/ ).

The genomic approach has accelerated the development of new cancer drugs. Indeed, two of the most relevant initiatives in recent years are ATOM (Accelerating Therapeutics for Opportunities in Medicine), which groups industry, government and academia, with the objective of accelerating the identification of drugs, 13 and the Connectivity Map (CMAP), a collection of transcriptional data obtained from cell lines treated with drugs for the discovery of functional connections between genes, diseases, and drugs. The CMAP 1.0 covered 1300 small molecules and more than 6000 signatures; meanwhile, the CMAP 2.0 with L1000 assay profiled more than 1.3 million samples and approximately 400 000 signatures. 14

The genomic study of tumors has had 2 fundamental contributions. On the one hand, it has allowed the confirmation and expansion of the concept of intratumor heterogeneity 15 , 16 ; and on the other, it has given rise to new classification systems for cancer. Based on the molecular classification developed by expression profiles, together with mutational and epigenomic profiles, a variety of molecular signatures have been identified, leading to the production of various commercial multigene panels. In breast cancer, for example, different panels have been developed, such as Pam50/Prosigna , Blue Print , OncotypeDX , MammaPrint , Prosigna , Endopredict , Breast Cancer Index , Mammostrat, and IHC4 . 17

Currently, the genomic/molecular study of cancer is more closely integrated with clinical practice, from the classification of neoplasms, as in tumors of the nervous system, 18 to its use in prediction, as in breast cancer. 17 Improvement in molecular methods and techniques has allowed the use of smaller amounts of biological material, as well as paraffin-embedded samples for genomic studies, both of which provide a wealth of information. 19 In addition, non-invasive methods, such as liquid biopsies, represent a great opportunity not only for the diagnosis of cancer, but also for follow-up, especially for unresectable tumors. 20

Research for the production of genomic information on cancer is presently dominated by several consortia, which has allowed the generation of a great quantity of data. However, most of these consortia and studies are performed in countries with a high human development index (HDI), and countries with a low HDI are not well represented in these large genomic studies. This is why initiatives such as Human Heredity and Health in Africa (H3Africa) for genomic research in Africa are essential. 21 Generation of new information and technological developments, such as third-generation sequencing, will undoubtedly continue to move forward in a multidisciplinary and complex systems context. However, the existing disparities in access to genomic tools for diagnosis, prognosis, and treatment of cancer will continue to be a pressing challenge at regional and social levels.

Cancer Epigenetics

Epigenetics studies the molecular mechanisms that produce hereditable changes in gene expression, without causing alterations in the DNA sequence. Epigenetic events are of 3 types: methylation of DNA and RNA, histone modification (acetylation, methylation, and phosphorylation), and the expression of non-coding RNA. Epigenetic aberrations can drive carcinogenesis when they alter chromosome conformation and the access to transcriptional machinery and to various regulatory elements (promoters, enhancers, and anchors for interaction with chromatin, for example). These changes may activate oncogenesis and silence tumor-suppressor mechanisms when they modulate coding and non-coding sequences (such as micro-RNAs and long-RNAs). This can then lead to uncontrolled growth, as well as the invasion and metastasis of cancer cells.

While genetic mutations are stable and irreversible, epigenetic alterations are dynamic and reversible; that is, there are several epigenomes, determined by space and time, which cause heterogeneity of the “epigenetic status” of tumors during their development and make them susceptible to environmental stimuli or chemotherapeutic treatment. 22 Epigenomic variability creates differences between cells, and this creates the need to analyze cells at the individual level. In the past, epigenetic analyses measured “average states” of cell populations. These studies revealed general mechanisms, such as the role of epigenetic marks on active or repressed transcriptional states, and established maps of epigenetic composition in a variety of cell types in normal and cancerous tissue. However, these approaches are difficult to use to examine events occurring in heterogeneous cell populations or in uncommon cell types. This has led to the development of new techniques that permit marking of a sequence on the epigenome and improvement in the recovery yield of epigenetic material from individual cells. This has helped to determine changes in DNA, RNA, and histones, chromatin accessibility, and chromosome conformation in a variety of neoplasms. 23 , 24

In cancer, DNA hypomethylation occurs on a global scale, while hypermethylation occurs in specific genomic loci, associated with abnormal nucleosome positioning and chromatin modifications. This information has allowed epigenomic profiles to be established in different types of neoplasms. In turn, these profiles have served as the basis to identify new neoplasm subgroups. For example, in triple negative breast cancer (TNBC), 25 and in hepatocellular carcinoma, 26 DNA methylation profiles have helped to the identification of distinct subgroups with clinical relevance. Epigenetic approaches have also helped to the development of prognostic tests to assess the sensitivity of cancer cells to specific drugs. 27

Epigenetic traits could be used to characterize intratumoral heterogeneity and determine the relevance of such a heterogeneity in clonal evolution and sensitivity to drugs. However, it is clear that heterogeneity is not only determined by genetic and epigenetic diversity resulting from clonal evolution of tumor cells, but also by the various cell populations that form the tumor microenvironment (TME). 28 Consequently, the epigenome of cancer cells is continually remodeled throughout tumorigenesis, during resistance to the activity of drugs, and in metastasis. 29 This makes therapeutic action based on epigenomic profiles difficult, although significant advances in this area have been reported. 30

During carcinogenesis and tumor progression, epigenetic modifications are categorized by their mechanisms of regulation ( Figure 1A ) and the various levels of structural complexity ( Figure 1B ). In addition, the epigenome can be modified by environmental stimuli, stochastic events, and genetic variations that impact the phenotype ( Figure 1C ). 31 , 32 The molecules that take part in these mechanisms/events/variations are therapeutic targets of interest with potential impact on clinical practice. There are studies on a wide variety of epidrugs, either alone or in combination, which improve antitumor efficacy. 33 However, the problems with these drugs must not be underestimated. For a considerable number of epigenetic compounds still being under study, the main challenge is to translate in vitro efficacy of nanomolar (nM) concentrations into well-tolerated and efficient clinical use. 34 The mechanisms of action of epidrugs may not be sufficiently controlled and could lead to diversion of the therapeutic target. 35 It is known that certain epidrugs, such as valproic acid, produce unwanted epigenetic changes 36 ; thus the need for a well-established safety profile before these drugs can be used in clinical therapy. Finally, resistance to certain epidrugs is another relevant problem. 37 , 38

Epigenetics of cancer. (A) Molecular mechanisms. (B) Structural hierarchy of epigenomics. (C) Factors affecting the epigenome. Modified from Refs. 31 and 32 .

As we learn about the epigenome of specific cell populations in cancer patients, a door opens to the evaluation of sensitivity tests and the search for new molecular markers for detection, prognosis, follow-up, and/or response to treatment at various levels of molecular regulation. Likewise, the horizon expands for therapeutic alternatives in oncology with the use of epidrugs, such as pharmacoepigenomic modulators for genes and key pathways, including methylation of promoters and regulation of micro-RNAs involved in chemoresponse and immune response in cancer. 39 There is no doubt that integrated approaches identifying stable pharmagenomic and epigenomic patterns and their relation with expression profiles and genetic functions will be more and more valuable in our fight against cancer.

Cancer Stem Cells

Tumors consist of different populations of neoplastic cells and a variety of elements that form part of the TME, including stromal cells and molecules of the extracellular matrix. 40 Such intratumoral heterogeneity becomes even more complex during clonal variation of transformed cells, as well as influence the elements of the TME have on these cells throughout specific times and places. 41 To explain the origin of cancer cell heterogeneity, 2 models have been put forward. The first proposes that mutations occur at random during development of the tumor in individual neoplastic cells, and this promotes the production of various tumor populations, which acquire specific growth and survival traits that lead them to evolve according to intratumor mechanisms of natural selection. 42 The second model proposes that each tumor begins as a single cell that possess 2 functional properties: it can self-renew and it can produce several types of terminal cells. As these 2 properties are characteristics of somatic stem cells, 43 the cells have been called cancer stem cells (CSCs). 44 According to this model, tumors must have a hierarchical organization, where self-renewing stem cells produce highly proliferating progenitor cells, unable to self-renew but with a high proliferation potential. The latter, in turn, give rise to terminal cells. 45 Current evidence indicates that both models may coexist in tumor progression. In agreement with this idea, new subclones could be produced as a result of a lack of genetic stability and mutational changes, in addition to the heterogeneity derived from the initial CSC and its descendants. Thus, in each tumor, a set of neoplastic cells with different genetic and epigenetic traits may be found, which would provide different phenotypic properties. 46

The CSC concept was originally presented in a model of acute myeloid leukemia. 47 The presence of CSCs was later proved in chronic myeloid leukemia, breast cancer, tumors of the central nervous system, lung cancer, colon cancer, liver cancer, prostate cancer, pancreatic cancer, melanoma, and cancer of the head and neck, amongst others. In all of these cases, detection of CSCs was based on separation of several cell populations according to expression of specific surface markers, such as CD133, CD44, CD24, CD117, and CD15. 48 It is noteworthy that in some solid tumors, and even in some hematopoietic ones, a combination of specific markers that allow the isolation of CSCs has not been found. Interestingly, in such tumors, a high percentage of cells with the capacity to start secondary tumors has been observed; thus, the terms Tumor Initiating Cells (TIC) or Leukemia Initiating Cells (LIC) have been adopted. 46

A relevant aspect of the biology of CSCs is that, just like normal stem cells, they can self-renew. Such self-renewal guarantees the maintenance or expansion of the tumor stem cell population. Another trait CSCs share with normal stem cells is their quiescence, first described in chronic myeloid leukemia. 49 The persistence of quiescent CSCs in solid tumors has been recently described in colorectal cancer, where quiescent clones can become dominant after therapy with oxaliplatin. 50 In non-hierarchical tumors, such as melanoma, the existence of slow-cycling cells that are resistant to antimitogenic agents has also been proved. 51 Such experimental evidence supports the idea that quiescent CSCs or TICs are responsible for both tumor resistance to antineoplastic drugs and clinical relapse after initial therapeutic success.

In addition to quiescence, CSCs use other mechanisms to resist the action of chemotherapeutic drugs. One of these is their increased numbers: upon diagnosis, a high number of CSCs are observed in most analyzed tumors, making treatment unable to destroy all of them. On the other hand, CSCs have a high number of molecular pumps that expulse drugs, as well as high numbers of antiapoptotic molecules. In addition, they have very efficient mechanisms to repair DNA damage. In general, these cells show changes in a variety of signaling pathways involved in proliferation, survival, differentiation, and self-renewal. It is worth highlighting that in recent years, many of these pathways have become potential therapeutic targets in the elimination of CSCs. 52 Another aspect that is highly relevant in understanding the biological behavior of CSCs is that they require a specific site for their development within the tissue where they are found that can provide whatever is needed for their survival and growth. These sites, known as niches, are made of various cells, both tumor and non-tumor, as well as a variety of non-cellular elements (extracellular matrix [ECM], soluble cytokines, ion concentration gradients, etc.), capable of regulating the physiology of CSCs in order to promote their expansion, the invasion of adjacent tissues, and metastasis. 53

It is important to consider that although a large number of surface markers have been identified that allow us to enrich and prospectively follow tumor stem cell populations, to this day there is no combination of markers that allows us to find these populations in all tumors, and it is yet unclear if all tumors present them. In this regard, it is necessary to develop new purification strategies based on the gene expression profiles of these cells, so that tumor heterogeneity is taken into account, as it is evident that a tumor can include multiple clones of CSCs that, in spite of being functional, are genetically different, and that these clones can vary throughout space (occupying different microenvironments and niches) and time (during the progression of a range of tumor stages). Such strategies, in addition to new in vitro and in vivo assays, will allow the development of new and improved CSC elimination strategies. This will certainly have an impact on the development of more efficient therapeutic alternatives.

Invasion and Metastasis

Nearly 90% of the mortality associated with cancer is related to metastasis. 54 This consists of a cascade of events ( Figure 2 ) that begins with the local invasion of a tumor into surrounding tissues, followed by intravasation of tumor cells into the blood stream or lymphatic circulation. Extravasation of neoplastic cells in areas distant from the primary tumor then leads to the formation of one or more micrometastatic lesions which subsequently proliferate to form clinically detectable lesions. 4 The cells that are able to produce metastasis must acquire migratory characteristics, which occur by a process known as epithelial–mesenchymal transition (EMT), that is, the partial loss of epithelial characteristics and the acquirement of mesenchymal traits. 55

Invasion and metastasis cascade. Invasion and metastasis can occur early or late during tumor progression. In either case, invasion to adjacent tissues is driven by stem-like cells (cancer stem cells) that acquire the epithelial–mesenchymal transition (EMT) (1). Once they reach sites adjacent to blood vessels, tumor cells (individually or in clusters) enter the blood (2). Tumor cells in circulation can adhere to endothelium and extravasation takes place (3). Other mechanisms alternative to extravasation can exist, such as angiopelosis, in which clusters of tumor cells are internalized by the endothelium. Furthermore, at certain sites, tumor cells can obstruct microvasculature and initiate a metastatic lesion right there. Sometimes, a tumor cells that has just exit circulation goes into an MET in order to become quiescent (4). Inflammatory signals can activate quiescent metastatic cells that will proliferate and generate a clinically detectable lesion (5).

Although several of the factors involved in this process are currently known, many issues are still unsolved. For instance, it has not yet been possible to monitor in vivo the specific moment when it occurs 54 ; the microenvironmental factors of the primary tumor that promote such a transition are not known with precision; and the exact moment during tumor evolution in which one cell or a cluster of cells begin to migrate to distant areas, is also unknown. The wide range of possibilities offered by intra- and inter-tumoral heterogeneity 56 stands in the way of suggesting a generalized strategy that could resolve this complication.

It was previously believed that metastasis was only produced in late stages of tumor progression; however, recent studies indicate that EMT and metastasis can occur during the early course of the disease. In pancreatic cancer, for example, cells going through EMT are able to colonize and form metastatic lesions in the liver in the first stages of the disease. 52 , 57 Metastatic cell clusters circulating in peripheral blood (PB) are prone to generate a metastatic site, compared to individual tumor cells. 58 , 59 In this regard, novel strategies, such as the use of micro-RNAs, are being assessed in order to diminish induction of EMT. 60 It must be mentioned, however, that the metastatic process seems to be even more complex, with alternative pathways that do not involve EMT. 61 , 62

A crucial stage in the process of metastasis is the intravasation of tumor cells (alone or in clusters) towards the blood stream and/or lymphatic circulation. 63 These mechanisms are also under intensive research because blocking them could allow the control of spreading of the primary tumor. In PB or lymphatic circulation, tumor cells travel to distant parts for the potential formation of a metastatic lesion. During their journey, these cells must stand the pressure of blood flow and escape interaction with natural killer (NK) cells . 64 To avoid them, tumor cells often cover themselves with thrombocytes and also produce factors such as VEGF, angiopoietin-2, angiopoietin-4, and CCL2 that are involved in the induction of vascular permeability. 54 , 65 Neutrophils also contribute to lung metastasis in the bloodstream by secreting IL-1β and metalloproteases to facilitate extravasation of tumor cells. 64

The next step in the process of metastasis is extravasation, for which tumor cells, alone or in clusters, can use various mechanisms, including a recently described process known as angiopellosis that involves restructuring the endothelial barrier to internalize one or several cells into a tissue. 66 The study of leukocyte extravasation has contributed to a more detailed knowledge of this process, in such a way that some of the proposed strategies to avoid extravasation include the use of integrin inhibitors, molecules that are vital for rolling, adhesion, and extravasation of tumor cells. 67 , 68 Another strategy that has therapeutic potential is the use of antibodies that strengthen vascular integrity to obstruct transendothelial migration of tumor cells and aid in their destruction in PB. 69

Following extravasation, tumor cells can return to an epithelial phenotype, a process known as mesenchymal–epithelial transition and may remain inactive for several years. They do this by competing for specialized niches, like those in the bone marrow, brain, and intestinal mucosa, which provide signals through the Notch and Wnt pathways. 70 Through the action of the Wnt pathway, tumor cells enter a slow state of the cell cycle and induce the expression of molecules that inhibit the cytotoxic function of NK cells. 71 The extravasated tumor cell that is in a quiescent state must comply with 2 traits typical of stem cells: they must have the capacity to self-renew and to generate all of the cells that form the secondary tumor.

There are still several questions regarding the metastatic process. One of the persisting debates at present is if EMT is essential for metastasis or if it plays a more important role in chemoresistance. 61 , 62 It is equally important to know if there is a pattern in each tumor for the production of cells with the capacity to carry out EMT. In order to control metastasis, it is fundamental to know what triggers acquisition of the migratory phenotype and the intrinsic factors determining this transition. Furthermore, it is essential to know if mutations associated with the primary tumor or the variety of epigenetic changes are involved in this process. 55 It is clear that metastatic cells have affinity for certain tissues, depending on the nature of the primary tumor (seed and soil hypothesis). This may be caused by factors such as the location and the direction of the bloodstream or lymphatic fluid, but also by conditioning of premetastatic niches at a distance (due to the large number of soluble factors secreted by the tumor and the recruitment of cells of the immune system to those sites). 72 We have yet to identify and characterize all of the elements that participate in this process. Deciphering them will be of upmost importance from a therapeutic point of view.

Epidemiology of Cancer

Cancer is the second cause of death worldwide; today one of every 6 deaths is due to a type of cancer. According to the International Agency for Research on Cancer (IARC), in 2020 there were approximately 19.3 million new cases of cancer, and 10 million deaths by this disease, 6 while 23.8 million cases and 13.0 million deaths are projected to occur by 2030. 73 In this regard, it is clear the increasing role that environmental factors—including environmental pollutants and processed food—play as cancer inducers and promoters. 74 The types of cancer that produce the greatest numbers of cases and deaths worldwide are indicated in Table 1 . 6

Total Numbers of Cancer Cases and Deaths Worldwide in 2020 by Cancer Type (According to the Global Cancer Observatory, IARC).

Data presented on this table were obtained from Ref. 6.

As shown in Figure 3 , lung, breast, prostate, and colorectal cancer are the most common throughout the world, and they are mostly concentrated in countries of high to very high human development index (HDI). Although breast, prostate, and colorectal cancer have a high incidence, the number of deaths they cause is proportionally low, mostly reflecting the great progress made in their control. However, these data also reveal the types of cancer that require further effort in prevention, precise early detection avoiding overdiagnosis, and efficient treatment. This is the case of liver, lung, esophageal, and pancreatic cancer, where the difference between the number of cases and deaths is smaller ( Figure 3B ). Social and economic transition in several countries has had an impact on reducing the incidence of neoplasms associated with infection and simultaneously produced an increase in the types related to reproductive, dietary, and hormonal factors. 75

Incidence and mortality for some types of cancer in the world. (A) Estimated number of cases and deaths in 2020 for the most frequent cancer types worldwide. (B) Incidence and mortality rates, normalized according to age, for the most frequent cancer types in countries with very high/& high (VH&H; blue) and/low and middle (L&M; red) Human Development Index (HDI). Data include both genders and all ages. Data according to https://gco.iarc.fr/today , as of June 10, 2021.

In the past 3 decades, cancer mortality rates have fallen in high HDI countries, with the exception of pancreatic cancer, and lung cancer in women. Nevertheless, changes in the incidence of cancer do not show the same consistency, possibly due to variables such as the possibility of early detection, exposure to risk factors, or genetic predisposition. 76 , 77 Countries such as Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the United Kingdom have reported a reduction in incidence and mortality in cancer of the stomach, colon, lung, and ovary, as well as an increase in survival. 78 Changes in modifiable risk factors, such as the use of tobacco, have played an important role in prevention. In this respect, it has been estimated that decline in tobacco use can explain between 35% and 45% of the reduction in cancer mortality rates, 79 while the fall in incidence and mortality due to stomach cancer can be attributed partly to the control of Helicobacter pylori infection. 80 Another key factor in the fall of mortality rates in developed countries has been an increase in early detection as a result of screening programs, as in breast and prostate cancer, which have had their mortality rates decreased dramatically in spite of an increase in their incidence. 76

Another important improvement observed in recent decades is the increase in survival rates, particularly in high HDI countries. In the USA, for example, survival rates for patients with prostate cancer at 5 years after initial diagnosis was 28% during 1947–1951; 69% during 1975–1977, and 100% during 2003–2009. Something similar occurred with breast cancer, with a 5-year survival rate of 54% in 1947–1951, 75% in 1975–1977, and 90% in 2003–2009. 81 In the CONCORD 3 version, age-standardize 5-year survival for patients with breast cancer in the USA during 2010–2014 was 90%, and 97% for prostate cancer patients. 82 Importantly, even among high HDI countries, significant differences have been identified in survival rates, being stage of disease at diagnosis, time for access to effective treatment, and comorbidities, the main factors influencing survival in these nations. 78 Unfortunately, survival rates in low HDI countries are significantly lower due to several factors, including lack of information, deficient screening and early detection programs, limited access to treatment, and suboptimal cancer registration. 82 It should be noted that in countries with low to middle HDI, neoplasms with the greatest incidence are those affecting women (breast and cervical cancer), which reflects not only a problem with access to health services, but also a serious inequality issue that involves social, cultural, and even religious obstacles. 83

Up to 42% of incident cases and 47% of deaths by cancer in the USA are due to potentially modifiable risk factors such as use of tobacco, physical activity, diet, and infection. 84 It has been calculated that 2.4 million deaths by cancer, mostly of the lung, can be attributed to tobacco. 73 In 2020, the incidence rate of lung cancer in Western Africa was 2.2, whereas in Polynesia and Eastern Asia was 37.3 and 34.4, respectively. 6 In contrast, the global burden of cancer associated with infection was 15.4%, but in Sub-Saharan Africa it was 30%. 85 Likewise, the incidence of cervical cancer in Eastern Africa was 40.1, in contrast with the USA and Canada that have a rate of 6.2. This makes it clear that one of the challenges we face is the reduction of the risk factors that are potentially modifiable and associated with specific types of cancer.

Improvement of survival rates and its disparities worldwide are also important challenges. Five-year survival for breast cancer—diagnosed during 2010-2014— in the USA, for example, was 90%, whereas in countries like South Africa it was 40%. 82 Childhood leukemia in the USA and several European countries shows a 5-year survival of 90%, while in Latin-American countries it is 50–76%. 86 Interestingly, there are neoplasms, such as pancreatic cancer, for which there has been no significant increase in survival, which remains low (5–15%) both in developed and developing countries. 82

Although data reported on global incidence and mortality gives a general overview on the epidemiology of cancer, it is important to note that there are great differences in coverage of cancer registries worldwide. To date, only 1 out of every 3 countries reports high quality data on the incidence of cancer. 87 For the past 50 years, the IARC has supported population-based cancer registries; however, more than one-third of the countries belonging to the WHO, mainly countries of low and middle income (LMIC), have no data on more than half of the 18 indicators of sustainable development goals. 88 High quality cancer registries only cover 4% of the population in Africa, 8% in Asia, and 7% in Latin America, contrasting with 83% in the USA and Canada, and 33% in Europe. 89 In response to this situation, the Global Initiative for Cancer Registry Development was created in 2012 to generate improved infrastructure to permit greater coverage and better quality registries, especially in countries with low and middle HDI. 88 It is expected that initiatives of this sort in the coming years will allow more and better information to guide strategies for the control of cancer worldwide, especially in developing regions. This will enable survival to be measured over longer periods of time (10, 15, or 20 years), as an effective measure in the control of cancer. The WHO has established as a target for 2025 to reduce deaths by cancer and other non-transmissible diseases by 25% in the population between the ages of 30–69; such an effort requires not only effective prevention measures to reduce incidence, but also more efficient health systems to diminish mortality and increase survival. At the moment, it is an even greater challenge because of the effects of the COVID-19 pandemic which has negatively impacted cancer prevention and health services. 90

Oncologic Treatments

A general perspective.

At the beginning of the 20th century, cancer treatment, specifically treatment of solid tumors, was based fundamentally on surgical resection of tumors, which together with other methods for local control, such as cauterization, had been used since ancient times. 91 At that time, there was an ongoing burst of clinical observations along with interventions sustained on fundamental knowledge about physics, chemistry, and biology. In the final years of the 19 th century and the first half of the 20th, these technological developments gave rise to radiotherapy, hormone therapy, and chemotherapy. 92 - 94 Simultaneously, immunotherapy was also developed, although usually on a smaller scale, in light of the overwhelming progress of chemotherapy and radiotherapy. 95

Thus began the development and expansion of disciplines based on these approaches (surgery, radiotherapy, chemotherapy, hormone therapy, and immunotherapy), with their application evolving ever more rapidly up to their current uses. Today, there is a wide range of therapeutic tools for the care of cancer patients. These include elements that emerged empirically, arising from observations of their effects in various medical fields, as well as drugs that were designed to block processes and pathways that form part of the physiopathology of one or more neoplasms according to knowledge of specific molecular alterations. A classic example of the first sort of tool is mustard gas, originally used as a weapon in war, 96 but when applied for medical purposes, marked the beginning of the use of chemicals in the treatment of malignant neoplasms, that is, chemotherapy. 94 A clear example of the second case is imatinib, designed specifically to selectively inhibit a molecular alteration in chronic myeloid leukemia: the Bcr-Abl oncoprotein. 97

It is on this foundation that today the 5 areas mentioned previously coexist and complement one another. The general framework that motivates this amalgam and guides its development is precision medicine, founded on the interaction of basic and clinical science. In the forecasts for development in each of these fields, surgery is expected to continue to be the fundamental approach for primary tumors in the foreseeable future, as well as when neoplastic disease in the patient is limited, or can be limited by applying systemic or regional elements, before and/or after surgical resection, and it can be reasonably anticipated for the patient to have a significant period free from disease or even to be cured. With regards to technology, intensive exploration of robotic surgery is contemplated. 98

The technological possibilities for radiotherapy have progressed in such a way that it is now possible to radiate neoplastic tissue with an extraordinary level of precision, and therefore avoid damage to healthy tissue. 99 This allows administration of large doses of ionizing radiation in one or a few fractions, what is known as “radiosurgery.” The greatest challenges to the efficacy of this approach are related to radio-resistance in certain neoplasms. Most efforts regarding research in this field are concentrated on understanding the underlying biological mechanisms of the phenomenon and their potential control through radiosensitizers. 100

“Traditional” chemotherapy, based on the use of compounds obtained from plants and other natural products, acting in a non-specific manner on both neoplastic and healthy tissues with a high proliferation rate, continues to prevail. 101 The family of chemotherapeutic drugs currently includes alkylating agents, antimetabolites, anti-topoisomerase agents, and anti-microtubules. Within the pharmacologic perspective, the objective is to attain a high concentration or activity of such molecules in specific tissues while avoiding their accumulation in others, in order to achieve an increase in effectiveness and a reduction in toxicity. This has been possible with the use of viral vectors, for example, that are able to limit their replication in neoplastic tissues, and activate prodrugs of normally nonspecific agents, like cyclophosphamide, exclusively in those specific areas. 102 More broadly, chemotherapy also includes a subgroup of substances, known as molecular targeted therapy, that affect processes in a more direct and specific manner, which will be mentioned later.

There is no doubt that immunotherapy—to be explored next—is one of the therapeutic fields where development has been greatest in recent decades and one that has produced enormous expectation in cancer treatment. 103 Likewise, cell therapy, based on the use of immune cells or stem cells, has come to complement the oncologic therapeutic arsenal. 43 Each and every one of the therapeutic fields that have arisen in oncology to this day continue to prevail and evolve. Interestingly, the foreseeable future for the development of cancer treatment contemplates these approaches in a joint and complementary manner, within the general framework of precision medicine, 104 and sustained by knowledge of the biological mechanisms involved in the appearance and progression of neoplasms. 105 , 106

Immunotherapy

Stimulating the immune system to treat cancer patients has been a historical objective in the field of oncology. Since the early work of William Coley 107 to the achievements reached at the end of the 20 th century, scientific findings and technological developments paved the way to searching for new immunotherapeutic strategies. Recombinant DNA technology allowed the synthesis of cytokines, such as interferon-alpha (IFN-α) and interleukin 2 (IL-2), which were authorized by the US Food and Drug Administration (FDA) for the treatment of hairy cell leukemia in 1986, 108 as well as kidney cancer and metastatic melanoma in 1992 and 1998, respectively. 109

The first therapeutic vaccine against cancer, based on the use of autologous dendritic cells (DCs), was approved by the FDA against prostate cancer in 2010. However, progress in the field of immunotherapy against cancer was stalled in the first decade of the present century, mostly due to failure of several vaccines in clinical trials. In many cases, application of these vaccines was detained by the complexity and cost involved in their production. Nevertheless, with the coming of the concept of immune checkpoint control, and the demonstration of the relevance of molecules such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), and programmed cell death molecule-1 (PD-1), immunotherapy against cancer recovered its global relevance. In 2011, the monoclonal antibody (mAb) ipilimumab, specific to the CTLA-4 molecule, was the first checkpoint inhibitor (CPI) approved for the treatment of advanced melanoma. 110 Later, inhibitory mAbs for PD-1, or for the PD-1 ligand (PD-L1), 111 as well as the production of T cells with chimeric receptors for antigen recognition (CAR-T), 112 which have been approved to treat various types of cancer, including melanoma, non-small cell lung cancer (NSCLC), head and neck cancer, bladder cancer, renal cell carcinoma (RCC), and hepatocellular carcinoma, among others, have changed the paradigm of cancer treatment.

In spite of the current use of anti-CTLA-4 and anti-PD-L1 mAbs, only a subgroup of patients has responded favorably to these CPIs, and the number of patients achieving clinical benefit is still small. It has been estimated that more than 70% of patients with solid tumors do not respond to CPI immunotherapy because either they show primary resistance, or after responding favorably, develop resistance to treatment. 113 In this regard, it is important to mention that in recent years very important steps have been taken to identify the intrinsic and extrinsic mechanisms that mediate resistance to CPI immunotherapy. 114 Intrinsic mechanisms include changes in the antitumor immune response pathways, such as faulty processing and presentation of antigens by APCs, activation of T cells for tumor cell destruction, and changes in tumor cells that lead to an immunosuppressive TME. Extrinsic factors include the presence of immunosuppressive cells in the local TME, such as regulatory T cells, myeloid-derived suppressor cells (MDSC), mesenchymal stem/stromal cells (MSCs), and type 2 macrophages (M2), in addition to immunosuppressive cytokines.

On the other hand, classification of solid tumors as “hot,” “cold,” or “excluded,” depending on T cell infiltrates and the contact of such infiltrates with tumor cells, as well as those that present high tumor mutation burden (TMB), have redirected immunotherapy towards 3 main strategies 115 ( Table 2 ): (1) Making T-cell antitumor response more effective, using checkpoint inhibitors complementary to anti-CTLA-4 and anti-PD-L1, such as LAG3, Tim-3, and TIGT, as well as using CAR-T cells against tumor antigens. (2) Activating tumor-associated myeloid cells including monocytes, granulocytes, macrophages, and DC lineages, found at several frequencies within human solid tumors. (3) Regulating the biochemical pathways in TME that produce high concentrations of immunosuppressive molecules, such as kynurenine, a product of tryptophan metabolism, through the activity of indoleamine 2,3 dioxygenase; or adenosine, a product of ATP hydrolysis by the activity of the enzyme 5’nucleotidase (CD73). 116

Current Strategies to Stimulate the Immune Response for Antitumor Immunotherapy.

Abbreviations: TME, tumor microenvironment; IL, interleukin; TNF, Tumor Necrosis Factor; TNFR, TNF-receptor; CD137, receptor–co-stimulator of the TNFR family; OX40, member number 4 of the TNFR superfamily; CD27/CD70, member of the TNFR superfamily; CD40/CD40L, antigen-presenting cells (APC) co-stimulator and its ligand; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; STING, IFN genes-stimulator; RIG-I, retinoic acid inducible gene-I; MDA5, melanoma differentiation-associated protein 5; CDN, cyclic dinucleotide; ATP, adenosine triphosphate; HMGB1, high mobility group B1 protein; TLR, Toll-like receptor; HVEM, Herpes virus entry mediator; GITR, glucocorticoid-induced TNFR family-related gene; CTLA4, cytotoxic T lymphocyte antigen 4; PD-L1, programmed death ligand-1; TIGIT, T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibition motives; CSF1/CSF1R, colony-stimulating factor-1 and its receptor; CCR2, Type 2 chemokine receptor; PI3Kγ, Phosphoinositide 3-Kinase γ; CXCL/CCL, chemokine ligands; LFA1, lymphocyte function-associated antigen 1; ICAM1, intercellular adhesion molecule 1; VEGF, vascular endothelial growth factor; IDO, indolamine 2,3-dioxigenase; TGF, transforming growth factor; LAG-3, lymphocyte-activation gene 3 protein; TIM-3, T-cell immunoglobulin and mucin-domain containing-3; CD73, 5´nucleotidase; ARs, adenosine receptors; Selectins, cell adhesion molecules; CAR-T, chimeric antigen receptor T cell; TCR-T, T-cell receptor engineered T cell.

Apart from the problems associated with its efficacy (only a small group of patients respond to it), immunotherapy faces several challenges related to its safety. In other words, immunotherapy can induce adverse events in patients, such as autoimmunity, where healthy tissues are attacked, or cytokine release syndrome and vascular leak syndrome, as observed with the use of IL-2, both of which lead to serious hypotension, fever, renal failure, and other adverse events that are potentially lethal. The main challenges to be faced by immunotherapy in the future will require the combined efforts of basic and clinical scientists, with the objective of accelerating the understanding of the complex interactions between cancer and the immune system, and improve treatment options for patients. Better comprehension of immune phenotypes in tumors, beyond the state of PD-L1 and TME, will be relevant to increase immunotherapy efficacy. In this context, the identification of precise tumor antigenicity biomarkers by means of new technologies, such as complete genome sequencing, single cell sequencing, and epigenetic analysis to identify sites or subclones typical in drug resistance, as well as activation, traffic and infiltration of effector cells of the immune response, and regulation of TME mechanisms, may help define patient populations that are good candidates for specific therapies and therapeutic combinations. 117 , 118 Likewise, the use of agents that can induce specific activation and modulation of the response of T cells in tumor tissue, will help improve efficacy and safety profiles that can lead to better clinical results.

Molecular Targeted Therapy

For over 30 years, and based on the progress in our knowledge of tumor biology and its mechanisms, there has been a search for therapeutic alternatives that would allow spread and growth of tumors to be slowed down by blocking specific molecules. This approach is known as molecular targeted therapy. 119 Among the elements generally used as molecular targets there are transcription factors, cytokines, membrane receptors, molecules involved in a variety of signaling pathways, apoptosis modulators, promoters of angiogenesis, and cell cycle regulators. 120

Imatinib, a tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia, became the first targeted therapy in the final years of the 1990s. 97 From then on, new drugs have been developed by design, and today more than 60 targeted therapies have been approved by the FDA for the treatment of a variety of cancers ( Table 3 ). 121 This has had a significant impact on progression-free survival and global survival in neoplasms such as non-small cell lung cancer, breast cancer, renal cancer, and melanoma.

FDA Approved Molecular Targeted Therapies for the Treatment of Solid Tumors.

Abbreviations: mAb, monoclonal antibody; ALK, anaplastic lymphoma kinase; CDK, cyclin-dependent kinase; CTLA-4, cytotoxic lymphocyte antigen-4; EGFR, epidermal growth factor receptor; FGFR, fibroblast growth factor receptor; GIST, gastrointestinal stroma tumor; mTOR, target of rapamycine in mammal cells; NSCLC, non-small cell lung carcinoma; PARP, poli (ADP-ribose) polimerase; PD-1, programmed death protein-1; PDGFR, platelet-derived growth factor receptor; PD-L1, programmed death ligand-1; ER, estrogen receptor; PR, progesterone receptor; TKR, tyrosine kinase receptors; SERM, selective estrogen receptor modulator; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor. Modified from Ref. [ 127 ].

Most drugs classified as targeted therapies form part of 2 large groups: small molecules and mAbs. The former are defined as compounds of low molecular weight (<900 Daltons) that act upon entering the cell. 120 Targets of these compounds are cell cycle regulatory proteins, proapoptotic proteins, or DNA repair proteins. These drugs are indicated based on histological diagnosis, as well as molecular tests. In this group there are multi-kinase inhibitors (RTKs) and tyrosine kinase inhibitors (TKIs), like sunitinib, sorafenib, and imatinib; cyclin-dependent kinase (CDK) inhibitors, such as palbociclib, ribociclib and abemaciclib; poli (ADP-ribose) polimerase inhibitors (PARPs), like olaparib and talazoparib; and selective small-molecule inhibitors, like ALK and ROS1. 122

As for mAbs, they are protein molecules that act on membrane receptors or extracellular proteins by interrupting the interaction between ligands and receptors, in such a way that they reduce cell replication and induce cytostasis. Among the most widely used mAbs in oncology we have: trastuzumab, a drug directed against the receptor for human epidermal growth factor-2 (HER2), which is overexpressed in a subgroup of patients with breast and gastric cancer; and bevacizumab, that blocks vascular endothelial growth factor and is used in patients with colorectal cancer, cervical cancer, and ovarian cancer. Other mAbs approved by the FDA include pembolizumab, atezolizumab, nivolumab, avelumab, ipilimumab, durvalumab, and cemiplimab. These drugs require expression of response biomarkers, such as PD-1 and PD-L1, and must also have several resistance biomarkers, such as the expression of EGFR, the loss of PTEN, and alterations in beta-catenin. 123

Because cancer is such a diverse disease, it is fundamental to have precise diagnostic methods that allow us to identify the most adequate therapy. Currently, basic immunohistochemistry is complemented with neoplastic molecular profiles to determine a more accurate diagnosis, and it is probable that in the near future cancer treatments will be based exclusively on molecular profiles. In this regard, it is worth mentioning that the use of targeted therapy depends on the existence of specific biomarkers that indicate if the patient will be susceptible to the effects of the drug or not. Thus, the importance of underlining that not all patients are susceptible to receive targeted therapy. In certain neoplasms, therapeutic targets are expressed in less than 5% of the diagnosed population, hindering a more extended use of certain drugs.

The identification of biomarkers and the use of new generation sequencing on tumor cells has shown predictive and prognostic relevance. Likewise, mutation analysis has allowed monitoring of tumor clone evolution, providing information on changes in canonic gene sequences, such as TP53, GATA3, PIK3CA, AKT1, and ERBB2; infrequent somatic mutations developed after primary treatments, like SWI-SNF and JAK2-STAT3; or acquired drug resistance mutations such as ESR1. 124 The study of mutations is vital; in fact, many of them already have specific therapeutic indications, which have helped select adequate treatments. 125

There is no doubt that molecular targeted therapy is one of the main pillars of precision medicine. However, it faces significant problems that often hinder obtaining better results. Among these, there is intratumor heterogeneity and differences between the primary tumor and metastatic sites, as well as intrinsic and acquired resistance to these therapies, the mechanisms of which include the presence of heterogeneous subclones, DNA hypermethylation, histone acetylation, and interruption of mRNA degradation and translation processes. 126 Nonetheless, beyond the obstacles facing molecular targeted therapy from a biological and methodological point of view, in the real world, access to genomic testing and specific drugs continues to be an enormous limitation, in such a way that strategies must be designed in the future for precision medicine to be possible on a global scale.

Cell Therapy

Another improvement in cancer treatment is the use of cell therapy, that is, the use of specific cells as therapeutic agents. This clinical procedure has 2 modalities: the first consists of replacing and regenerating functional cells in a specific tissue by means of stem/progenitor cells of a certain kind, 43 while the second uses immune cells as effectors to eliminate malignant cells. 127

Regarding the first type, we must emphasize the development of cell therapy based on hematopoietic stem and progenitor cells. 128 For over 50 years, hematopoietic cell transplants have been used to treat a variety of hematologic neoplasms (different forms of leukemia and lymphoma). Today, it is one of the most successful examples of cell therapy, including innovative modalities, such as haploidentical transplants, 129 as well as application of stem cells expanded ex vivo . 130 There are also therapies that have used immature cells that form part of the TME, such as MSCs. The replication potential and cytokine secretion capacity of these cells make them an excellent option for this type of treatment. 131 Neural stem cells can also be manipulated to produce and secrete apoptotic factors, and when these cells are incorporated into primary neural tumors, they cause a certain degree of regression. They can even be transfected with genes that encode for oncolytic enzymes capable of inducing regression of glioblastomas. 132

With respect to cell therapy using immune cells, several research groups have manipulated cells associated with tumors to make them effector cells and thus improve the efficacy and specificity of the antitumor treatment. PB leckocytes cultured in the presence of IL-2 to obtain activated lymphocytes, in combination with IL-2 administration, have been used in antitumor clinical protocols. Similarly, infiltrating lymphocytes from tumors with antitumor activity have been used and can be expanded ex vivo with IL-2. These lymphocyte populations have been used in immunomodulatory therapies in melanoma, and pancreatic and kidney tumors, producing a favorable response in treated patients. 133 NK cells and macrophages have also been used in immunotherapy, although with limited results. 134 , 135

One of the cell therapies with better projection today is the use of CAR-T cells. This strategy combines 2 forms of advanced therapy: cell therapy and gene therapy. It involves the extraction of T cells from the cancer patient, which are genetically modified in vitro to express cell surface receptors that will recognize antigens on the surface of tumor cells. The modified T cells are then reintroduced in the patient to aid in an exacerbated immune response that leads to eradication of the tumor cells ( Figure 4 ). Therapy with CAR-T cells has been used successfully in the treatment of some types of leukemia, lymphoma, and myeloma, producing complete responses in patients. 136

CAR-T cell therapy. (A) T lymphocytes obtained from cancer patients are genetically manipulated to produce CAR-T cells that recognize tumor cells in a very specific manner. (B) Interaction between CAR molecule and tumor antigen. CAR molecule is a receptor that results from the fusion between single-chain variable fragments (scFv) from a monoclonal antibody and one or more intracellular signaling domains from the T-cell receptor. CD3ζ, CD28 and 4-1BB correspond to signaling domains on the CAR molecule.

Undoubtedly, CAR-T cell therapy has been truly efficient in the treatment of various types of neoplasms. However, this therapeutic strategy can also have serious side effects, such as release of cytokines into the bloodstream, which can cause different symptoms, from high fever to multiorgan failure, and even neurotoxicity, leading to cerebral edema in many cases. 137 Adequate control of these side effects is an important medical challenge. Several research groups are trying to improve CAR-T cell therapy through various approaches, including production of CAR-T cells directed against a wider variety of tumor cell-specific antigens that are able to attack different types of tumors, and the identification of more efficient types of T lymphocytes. Furthermore, producing CAR-T cells from a single donor that may be used in the treatment of several patients would reduce the cost of this sort of personalized cell therapy. 136

Achieving wider use of cell therapy in oncologic diseases is an important challenge that requires solving various issues. 138 One is intratumor cell heterogeneity, including malignant subclones and the various components of the TME, which results in a wide profile of membrane protein expression that complicates finding an ideal tumor antigen that allows specific identification (and elimination) of malignant cells. Likewise, structural organization of the TME challenges the use of cell therapy, as administration of cell vehicles capable of recognizing malignant cells might not be able to infiltrate the tumor. This results from low expression of chemokines in tumors and the presence of a dense fibrotic matrix that compacts the inner tumor mass and avoids antitumor cells from infiltrating and finding malignant target cells.

Further Challenges in the 21st Century

Beyond the challenges regarding oncologic biomedical research, the 21 st century is facing important issues that must be solved as soon as possible if we truly wish to gain significant ground in our fight against cancer. Three of the most important have to do with prevention, early diagnosis, and access to oncologic medication and treatment.

Prevention and Early Diagnosis

Prevention is the most cost-effective strategy in the long term, both in low and high HDI nations. Data from countries like the USA indicate that between 40-50% of all types of cancer are preventable through potentially modifiable factors (primary prevention), such as use of tobacco and alcohol, diet, physical activity, exposure to ionizing radiation, as well as prevention of infection through access to vaccination, and by reducing exposure to environmental pollutants, such as pesticides, diesel exhaust particles, solvents, etc. 74 , 84 Screening, on the other hand, has shown great effectiveness as secondary prevention. Once population-based screening programs are implemented, there is generally an initial increase in incidence; however, in the long term, a significant reduction occurs not only in incidence rates, but also in mortality rates due to detection of early lesions and timely and adequate treatment.

A good example is colon cancer. There are several options for colon cancer screening, such as detection of fecal occult blood, fecal immunohistochemistry, flexible sigmoidoscopy, and colonoscopy, 139 , 140 which identify precursor lesions (polyp adenomas) and allow their removal. Such screening has allowed us to observe 3 patterns of incidence and mortality for colon cancer between the years 2000 and 2010: on one hand, an increase in incidence and mortality in countries with low to middle HDI, mainly countries in Asia, South America, and Eastern Europe; on the other hand, an increase in incidence and a fall in mortality in countries with very high HDI, such as Canada, the United Kingdom, Denmark, and Singapore; and finally a fall in incidence and mortality in countries like the USA, Japan, and France. The situation in South America and Asia seems to reflect limitations in medical infrastructure and a lack of access to early detection, 141 while the patterns observed in developed countries reveal the success, even if it may be partial, of that which can be achieved by well-structured prevention programs.

Another example of success, but also of strong contrast, is cervical cancer. The discovery of the human papilloma virus (HPV) as the causal agent of cervical cancer brought about the development of vaccines and tests to detect oncogenic genotypes, which modified screening recommendations and guidelines, and allowed several developed countries to include the HPV vaccine in their national vaccination programs. Nevertheless, the outlook is quite different in other areas of the world. Eighty percent of the deaths by cervical cancer reported in 2018 occurred in low-income nations. This reveals the urgency of guaranteeing access to primary and secondary prevention (vaccination and screening, respectively) in these countries, or else it will continue to be a serious public health problem in spite of its preventability.

Screening programs for other neoplasms, such as breast, prostate, lung, and thyroid cancer have shown outlooks that differ from those just described, because, among other reasons, these neoplasms are highly diverse both biologically and clinically. Another relevant issue is the overdiagnosis of these neoplasms, that is, the diagnosis of disease that would not cause symptoms or death in the patient. 142 It has been calculated that 25% of breast cancer (determined by mammogram), 50–60% of prostate cancer (determined by PSA), and 13–25% of lung cancer (determined by CT) are overdiagnosed. 142 Thus, it is necessary to improve the sensitivity and specificity of screening tests. In this respect, knowledge provided by the biology of cancer and “omic” sciences offers a great opportunity to improve screening and prevention strategies. All of the above shows that prevention and early diagnosis are the foundations in the fight against cancer, and it is essential to continue to implement broader screening programs and better detection methods.

Global Equity in Oncologic Treatment

Progress in cancer treatment has considerably increased the number of cancer survivors. Nevertheless, this tendency is evident only in countries with a very solid economy. Indeed, during the past 30 years, cancer mortality rates have increased 30% worldwide. 143 Global studies indicate that close to 70% of cancer deaths in the world occur in nations of low to middle income. But even in high-income countries, there are sectors of society that are more vulnerable and have less access to cancer treatments. 144 Cancer continues to be a disease of great social inequality.

In Europe, the differences in access to cancer treatment are highly marked. These treatments are more accessible in Western Europe than in its Eastern counterpart. 145 Furthermore, highly noticeable differences between high-income countries have been detected in the cost of cancer drugs. 146 It is interesting to note that in many of these cases, treatment is too costly and the clinical benefit only marginal. Thus, the importance of these problems being approached by competent national, regional, and global authorities, because if these new drugs and therapeutic programs are not accessible to the majority, progress in biomedical, clinical and epidemiological research will have a limited impact in our fight against cancer. We must not forget that health is a universal right, from which low HDI countries must not be excluded, nor vulnerable populations in nations with high HDI. The participation of a well-informed society will also be fundamental to achieve a global impact, as today we must fight not only against the disease, but also against movements and ideas (such as the anti-vaccine movement and the so-called miracle therapies) that can block the medical battle against cancer.

Final Comments

From the second half of the 20th century to the present day, progress in our knowledge about the origin and development of cancer has been extraordinary. We now understand cancer in detail in genomic, molecular, cellular, and physiological terms, and this knowledge has had a significant impact in the clinic. There is no doubt that a patient who is diagnosed today with a type of cancer has a better prospect than a patient diagnosed 20 or 50 years ago. However, we are still far from winning the war against cancer. The challenges are still numerous. For this reason, oncologic biomedical research must be a worldwide priority. Likewise, one of the fundamental challenges for the coming decades must be to reduce unequal access to health services in areas of low- to middle income, and in populations that are especially vulnerable, as well as continue improving prevention programs, including public health programs to reduce exposure to environmental chemicals and improve diet and physical activity in the general population. 74 , 84 Fostering research and incorporation of new technological resources, particularly in less privileged nations, will play a key role in our global fight against cancer.

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Hector Mayani https://orcid.org/0000-0002-2483-3782