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Brain Cancer

Disease Details

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Description: Brain cancer is a malignant growth of abnormal cells in the brain, which can disrupt normal brain function.
Type: Brain cancer can manifest in several types, including gliomas (such as astrocytomas, glioblastomas, and oligodendrogliomas), meningiomas, medulloblastomas, and ependymomas, among others.

The type of genetic transmission in brain cancer can vary. Most cases of brain cancer are sporadic, meaning they occur due to mutations that are acquired during a person's life and are not inherited. However, a smaller proportion of brain cancers can be hereditary, occurring as a result of inherited genetic mutations. Hereditary conditions that increase the risk of brain cancer include neurofibromatosis types 1 and 2, Li-Fraumeni syndrome, and Von Hippel-Lindau disease.
Signs And Symptoms: The signs and symptoms of brain tumors are broad. People may experience symptoms regardless of whether the tumor is benign (not cancerous) or cancerous. Primary and secondary brain tumors present with similar symptoms, depending on the location, size, and rate of growth of the tumor. For example, larger tumors in the frontal lobe can cause changes in the ability to think. However, a smaller tumor in an area such as Wernicke's area (small area responsible for language comprehension) can result in a greater loss of function.
Prognosis: The prognosis of brain cancer depends on the type of cancer diagnosed. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma has a median survival of only 15 months even with aggressive chemoradiotherapy and surgery. Brainstem gliomas have the poorest prognosis of any form of brain cancer, with most patients dying within one year, even with therapy that typically consists of radiation to the tumor along with corticosteroids. However, one type, focal brainstem gliomas in children, seems open to exceptional prognosis and long-term survival has frequently been reported.Prognosis is also affected by presentation of genetic mutations. Certain mutations provide better prognosis than others. IDH1 and IDH2 mutations in gliomas, as well as deletion of chromosome arms 1p and 19q, generally indicate better prognosis. TP53, ATRX, EGFR, PTEN, and TERT mutations are also useful in determining prognosis.
Onset: The onset of brain cancer can vary widely depending on the type and location of the tumor. Symptoms may develop gradually over time or suddenly, and can include headaches, seizures, vision or speech difficulties, changes in personality, and cognitive or motor impairments. Early detection and diagnosis are crucial for effective treatment.
Prevalence: The prevalence of brain cancer varies by type and region. In the United States, an estimated 700,000 people are living with primary brain and central nervous system tumors. Primary brain tumors account for about 1.4% of all new cancer cases, with glioblastoma being the most common malignant type. The overall incidence rate is approximately 7 per 100,000 people per year. Prevalence can differ globally due to varying risk factors and diagnostic capabilities.
Epidemiology: Figures for incidences of cancers of the brain show a significant difference between more- and less-developed countries (the less-developed countries have lower incidences of tumors of the brain). This could be explained by undiagnosed tumor-related deaths (patients in extremely poor situations do not get diagnosed, simply because they do not have access to the modern diagnostic facilities required to diagnose a brain tumor) and by deaths caused by other poverty-related causes that preempt a patient's life before tumors develop or tumors become life-threatening. Nevertheless, statistics suggest that certain forms of primary brain tumors are more common among certain populations.The incidence of low-grade astrocytoma has not been shown to vary significantly with nationality. However, studies examining the incidence of malignant central nervous system (CNS) tumors have shown some variation with national origin. Since some high-grade lesions arise from low-grade tumors, these trends are worth mentioning. Specifically, the incidence of CNS tumors in the United States, Israel, and the Nordic countries is relatively high, while Japan and Asian countries have a lower incidence. These differences probably reflect some biological differences as well as differences in pathologic diagnosis and reporting.
Worldwide data on incidence of cancer can be found at the WHO (World Health Organization) and is handled by the IARC (International Agency for Research on Cancer) located in France.
Intractability: Brain cancer can be highly intractable, particularly aggressive forms such as glioblastoma. Intractability refers to the difficulty in effectively treating or managing the disease, and brain cancer often presents significant challenges. These challenges include the tumor's location, the blood-brain barrier's restriction on drug delivery, and the cancer's potential resistance to treatment. While some types may respond to surgery, radiation, or chemotherapy, many brain cancers remain difficult to treat successfully, and long-term prognosis can be poor.
Disease Severity: **Disease Severity:**
Brain cancer severity can vary widely based on the type, location, and stage of the tumor. Some brain cancers, such as glioblastomas, are highly aggressive and have poor prognosis, while others, like some low-grade gliomas, may have a relatively better outcome with proper treatment. Overall severity also depends on the cancer's impact on neurological functions and the patient's overall health.

**NAN (Nil Affected Nodes):**
Brain cancer staging does not typically involve lymph nodes in the same way as many other cancers, because the brain and spinal cord do not have a well-developed lymphatic system. Therefore, the concept of affected nodes (NAN) is not usually applicable in brain cancer staging. The focus is more on the size, location, and potential spread within the central nervous system.
Healthcare Professionals: Disease Ontology ID - DOID:1319
Pathophysiology: Pathophysiology of brain cancer includes the uncontrolled division and growth of abnormal cells in the brain. These cells can originate in the brain (primary brain cancer) or spread to the brain from other parts of the body (secondary or metastatic brain cancer). The abnormal cell growth disrupts normal brain function by invading and destroying healthy tissue, increasing intracranial pressure, and inducing inflammation. Tumors can interfere with the brain's electrical activity, leading to neurological deficits such as seizures, cognitive impairment, and physical disabilities. The underlying genetic mutations and molecular mechanisms can vary, involving alterations in oncogenes, tumor suppressor genes, and signaling pathways that regulate cell proliferation, apoptosis, and DNA repair.
Carrier Status: Brain cancer is not typically associated with a carrier status like some genetic disorders. It generally results from genetic mutations that can occur spontaneously or due to environmental factors. Some rare inherited syndromes, such as Li-Fraumeni syndrome or neurofibromatosis, can increase the risk of brain cancer, but these account for a small percentage of cases.
Mechanism: Brain cancer, particularly gliomas, develops through complex mechanisms involving genetic and epigenetic changes. Key molecular mechanisms include:

1. **Genetic Mutations:**
- Mutations in oncogenes (e.g., EGFR, PDGFRA) lead to uncontrolled cell proliferation.
- Tumor suppressor genes (e.g., TP53, PTEN) may be inactivated, removing normal growth constraints.

2. **Signal Transduction Pathways:**
- Abnormal activation of pathways such as PI3K/AKT/mTOR and RAS/MAPK promotes survival, growth, and resistance to apoptosis (programmed cell death).

3. **Epigenetic Changes:**
- DNA methylation and histone modification alterations can silence tumor suppressor genes or activate oncogenes without changing the DNA sequence.

4. **Gene Amplification:**
- Amplification of genes like EGFR can result in overexpression, enhancing proliferative signals.

5. **Tumor Microenvironment:**
- Interaction with the surrounding cells and extracellular matrix can facilitate tumor growth and invasion. This includes angiogenesis, the formation of new blood vessels, often driven by VEGF.

6. **Stem Cell-like Properties:**
- A subpopulation of cells with stem cell-like characteristics contributes to tumor initiation, heterogeneity, and resistance to conventional therapies.

Understanding these mechanisms helps in developing targeted therapies specific to the molecular alterations of the tumor.
Treatment: A medical team generally assesses the treatment options and presents them to the person affected and their family. Various types of treatment are available depending on tumor type and location, and may be combined to produce the best chances of survival:
Surgery: complete or partial resection of the tumor with the objective of removing as many tumor cells as possible.
Radiotherapy: the most commonly used treatment for brain tumors; the tumor is irradiated with beta, x rays or gamma rays.
Chemotherapy: a treatment option for cancer, however, it is not always used to treat brain tumors as the blood–brain barrier can prevent some drugs from reaching the cancerous cells.
A variety of experimental therapies are available through clinical trials.Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical removal and other factors specific to each case.Standard care for anaplastic oligodendrogliomas and anaplastic oligoastrocytomas is surgery followed by radiotherapy. One study found a survival benefit for the addition of chemotherapy to radiotherapy after surgery, compared with radiotherapy alone.
Compassionate Use Treatment: Compassionate use treatment for brain cancer refers to providing patients access to investigational drugs, biologics, or medical devices that are not yet approved by regulatory agencies but may offer potential benefits. This is typically considered when standard treatments have failed, and the patient has no other treatment options.

Off-label or experimental treatments for brain cancer may include:

1. **Bevacizumab (Avastin)**: Although primarily approved for other types of cancers, it's sometimes used off-label for treating recurrent glioblastoma.
2. **Tumor Treating Fields (Optune)**: This FDA-approved device generates electric fields to disrupt cancer cell division and has shown promise in treating glioblastoma.
3. **Nivolumab (Opdivo) and Pembrolizumab (Keytruda)**: These immune checkpoint inhibitors are approved for other cancers and are being investigated in clinical trials for brain tumors.
4. **Oncolytic virus therapy**: Experimental treatments using modified viruses to selectively infect and kill cancer cells are being tested.
5. **CAR-T cell therapy**: Chimeric Antigen Receptor T-cell therapy is largely experimental for brain cancer but involves engineering a patient's immune cells to target cancer cells.
6. **Gene therapy**: Various gene therapy approaches aim to introduce genetic material into cells to combat or prevent the disease.
7. **Precision medicine**: Tailoring treatment based on the genetic profile of the patient's tumor is an emerging field, often involving a combination of targeted therapies.
Lifestyle Recommendations: For individuals diagnosed with brain cancer, certain lifestyle recommendations may help improve overall well-being and complement medical treatments:

1. **Healthy Diet**: Consume a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats to support immune function and energy levels.

2. **Regular Exercise**: Engage in low-impact physical activities, such as walking or yoga, to enhance physical fitness and mental health, as tolerated and advised by a healthcare provider.

3. **Stress Management**: Practice stress-reducing techniques like meditation, deep breathing exercises, or mindfulness to improve emotional well-being.

4. **Adequate Sleep**: Ensure sufficient and quality sleep to help the body recover and maintain overall health.

5. **Avoid Tobacco and Limit Alcohol**: Refrain from smoking and limit alcohol consumption, as these can negatively impact health and interfere with treatment efficacy.

6. **Stay Hydrated**: Drink plenty of fluids to stay hydrated, which is crucial for overall health and managing side effects of treatments.

7. **Support Systems**: Seek emotional and psychological support through counseling, support groups, or talking with family and friends.

Always consult with healthcare professionals before making any significant changes to lifestyle, especially when undergoing treatment for brain cancer.
Medication: Medications for brain cancer can vary based on the type and stage of the cancer, as well as the patient's overall health. Commonly used medications include:

1. **Temozolomide (Temodar):** Often used as a first-line treatment for glioblastoma.
2. **Bevacizumab (Avastin):** Used to inhibit angiogenesis, the development of new blood vessels that tumors need to grow.
3. **Carmustine (BiCNU):** A type of chemotherapy used for brain tumors.
4. **Lomustine (Gleostine):** Another chemotherapy drug often used for brain tumors.
5. **Steroids (e.g., Dexamethasone):** Used to reduce inflammation and swelling around tumors.

Medications may be used in combination with surgery, radiation therapy, and other treatments. Treatment regimens are usually personalized based on individual patient factors.
Repurposable Drugs: Repurposable drugs for brain cancer include:

1. **Metformin**: Originally used for type 2 diabetes, it has shown potential anti-tumor effects.
2. **Chloroquine/Hydroxychloroquine**: These antimalarial drugs have been studied for their ability to inhibit autophagy in cancer cells.
3. **Valproic Acid**: Commonly used as an anticonvulsant and mood stabilizer, it may have efficacy due to its histone deacetylase inhibition properties.
4. **Aspirin**: Known for its anti-inflammatory properties, it has been researched for its potential anti-cancer effects.
5. **Statins**: These cholesterol-lowering drugs have shown promise in inhibiting tumor growth and promoting cancer cell apoptosis.

These drugs are being researched for their effectiveness against various forms of brain cancer, including glioblastomas.
Metabolites: Brain cancer, a complex and aggressive disease, involves altered metabolism. Metabolites such as lactate, glutamine, and choline can be elevated in brain cancer cells due to changes in energy production and biosynthesis. Elevated lactate is often a result of increased glycolysis (the Warburg effect), glutamine serves as a crucial nutrient for cell growth, and choline is involved in membrane synthesis. Nanoparticle-based approaches (often abbreviated as "nan") are being researched for their potential to improve the diagnosis and treatment of brain cancer, including targeted drug delivery and imaging for more precise tumor localization.
Nutraceuticals: For brain cancer, nutraceuticals are studied for their potential to support conventional treatments and improve patient outcomes. Certain compounds like curcumin, resveratrol, and green tea polyphenols have shown promise in preclinical studies for their anti-inflammatory and antioxidant properties. However, their effectiveness and safety in human trials are still under investigation.

Nanotechnology offers innovative approaches for brain cancer treatment. Nanoparticles can be engineered to deliver drugs directly to tumor cells, potentially enhancing the efficacy of chemotherapy and reducing side effects. Additionally, nanoparticles can be designed for imaging purposes, providing better diagnostic capabilities and monitoring of treatment responses.

Further research is crucial to fully understand the benefits and risks of nutraceuticals and nanotechnology in brain cancer treatment.
Peptides: Peptides and nanoparticles (nan) represent emerging areas of research in the treatment of brain cancer.

**Peptides:** These are short chains of amino acids that can be used to deliver drugs, target specific cancer cells, or modulate signaling pathways involved in tumor growth. Peptide-based therapies aim to improve the specificity and efficacy of treatments while minimizing side effects.

**Nanoparticles:** These are extremely small particles that can be engineered to carry drugs directly to tumor sites, enhancing the concentration of the therapeutic agent in the cancerous area while reducing systemic toxicity. Nanoparticles can also be designed to bypass the blood-brain barrier, which is a significant challenge in treating brain cancer.

Both peptides and nanoparticles hold promise for more effective and targeted therapies in brain cancer, potentially improving outcomes and reducing side effects compared to conventional treatments.