Glioblastoma
Disease Details
Family Health Simplified
- Description
- Glioblastoma is an aggressive and malignant type of brain tumor that originates from glial cells.
- Type
- Glioblastoma is a type of primary brain tumor classified as a grade IV astrocytoma. It is highly aggressive and malignant. The type of genetic transmission for glioblastoma is typically sporadic, meaning it usually occurs due to random mutations in the cells rather than being inherited. However, in rare cases, it can be associated with certain inherited genetic syndromes like Li-Fraumeni syndrome or Turcot syndrome.
- Signs And Symptoms
- Common symptoms include seizures, headaches, nausea and vomiting, memory loss, changes to personality, mood or concentration, and localized neurological problems. The kinds of symptoms produced depend more on the location of the tumor than on its pathological properties. The tumor can start producing symptoms quickly, but occasionally is an asymptomatic condition until it reaches an enormous size.
- Prognosis
- The most common length of survival following diagnosis is 10 to 13 months (although recent research points to a median survival rate of 15 months), with fewer than 1–3% of people surviving longer than five years. In the United States between 2012 and 2016 five-year survival was 6.8%. Without treatment, survival is typically three months. Complete cures are extremely rare, but have been reported.Increasing age (> 60 years) carries a worse prognostic risk. Death is usually due to widespread tumor infiltration with cerebral edema and increased intracranial pressure.A good initial Karnofsky performance score (KPS) and MGMT methylation are associated with longer survival. A DNA test can be conducted on glioblastomas to determine whether or not the promoter of the MGMT gene is methylated. Patients with a methylated MGMT promoter have longer survival than those with an unmethylated MGMT promoter, due in part to increased sensitivity to temozolomide.Long-term benefits have also been associated with those patients who receive surgery, radiotherapy, and temozolomide chemotherapy. However, much remains unknown about why some patients survive longer with glioblastoma. Age under 50 is linked to longer survival in GBM, as is 98%+ resection and use of temozolomide chemotherapy and better KPSs. A recent study confirms that younger age is associated with a much better prognosis, with a small fraction of patients under 40 years of age achieving a population-based cure. Cure is thought to occur when a person's risk of death returns to that of the normal population, and in GBM, this is thought to occur after 10 years.UCLA Neuro-oncology publishes real-time survival data for patients with this diagnosis.According to a 2003 study, GBM prognosis can be divided into three subgroups dependent on KPS, the age of the patient, and treatment.
- Onset
- Glioblastoma, also known as glioblastoma multiforme (GBM), is an aggressive type of brain tumor. The onset of symptoms can be sudden or gradual, depending on the location and growth rate of the tumor. Common symptoms include headaches, seizures, neurological deficits (such as weakness or speech problems), and cognitive or personality changes. The median age of onset is around 64 years old.
- Prevalence
- Glioblastoma is a rare but aggressive type of brain tumor. It accounts for approximately 14.5% of all primary brain and central nervous system tumors and 48.6% of malignant brain tumors. The annual incidence rate of glioblastoma in the United States is about 3.19 per 100,000 people.
- Epidemiology
- About three per 100,000 people develop the disease a year, although regional frequency may be much higher. The frequency in England doubled between 1995 and 2015.It is the second-most common central nervous system tumor after meningioma. It occurs more commonly in males than females. Although the average age at diagnosis is 64, in 2014, the broad category of brain cancers was second only to leukemia in people in the United States under 20 years of age.
- Intractability
- Glioblastoma is considered highly intractable. This aggressive brain tumor is difficult to treat due to its rapid growth, invasive nature, and resistance to conventional therapies. Despite advances in surgery, radiation, and chemotherapy, the prognosis remains poor, with median survival often less than 15 months after diagnosis.
- Disease Severity
- Glioblastoma is an aggressive and highly malignant form of brain cancer. It is considered one of the most severe types of brain tumors due to its rapid growth and tendency to infiltrate surrounding brain tissue, which makes complete surgical removal challenging. The prognosis for glioblastoma patients is generally poor, with a median survival rate typically ranging from 12 to 15 months despite intensive treatment involving surgery, radiation, and chemotherapy. The severity of the disease is compounded by its resistance to conventional therapies and high recurrence rates.
- Healthcare Professionals
- Disease Ontology ID - DOID:3068
- Pathophysiology
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Glioblastoma, also known as glioblastoma multiforme (GBM), is an aggressive type of cancer that occurs in the brain or spinal cord. The pathophysiology of glioblastoma involves several key aspects:
1. **Cell Origin**: Glioblastomas originate from astrocytes, which are star-shaped glial cells in the central nervous system. They are classified as Grade IV astrocytomas, indicating a high degree of malignancy.
2. **Genetic Abnormalities**: Genetic mutations and alterations play a crucial role, including:
- Mutations in the **TP53** gene, which is critical for DNA repair and apoptosis.
- Amplification of the **EGFR** gene, leading to overactive cell signaling and proliferation.
- Loss of heterozygosity on chromosome 10, particularly affecting the **PTEN** gene, which normally suppresses tumor growth.
3. **Cellular Proliferation**: Rapid and uncontrollable proliferation of malignant astrocytes is a hallmark. This results in highly cellular and heterogeneous tumors with regions of necrosis (dead cells) due to insufficient blood supply.
4. **Angiogenesis**: Glioblastomas are highly vascular tumors that stimulate the formation of new blood vessels (angiogenesis) to supply the growing tumor. This is mediated by factors like VEGF (vascular endothelial growth factor).
5. **Invasion and Infiltration**: These tumors are highly invasive, often infiltrating surrounding brain tissue, which makes complete surgical resection difficult. The infiltrative nature arises from the tumor cells' ability to migrate along blood vessels and white matter tracts.
6. **Microenvironment**: The tumor creates a unique microenvironment that supports its growth and protects it from the immune system. This includes hypoxic (low oxygen) areas that promote tumor resilience and progression.
Understanding these pathophysiological mechanisms is crucial for developing targeted therapies and improving outcomes for patients with glioblastoma. - Carrier Status
- Glioblastoma is not known to have a carrier status. It is a type of primary brain cancer that typically arises sporadically, meaning it usually occurs in individuals without a family history or inherited genetic mutation associated with the disease. It is most often caused by a combination of genetic mutations and environmental factors rather than being inherited.
- Mechanism
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Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive type of primary brain tumor.
**Mechanism:**
Glioblastoma arises from astrocytes, which are star-shaped glial cells in the brain. The tumor is highly invasive, infiltrating surrounding brain tissue, which makes complete surgical removal difficult. It is characterized by rapid growth and a tendency to form new blood vessels (angiogenesis) to support its nutritional needs.
**Molecular Mechanisms:**
1. **Genetic Mutations:**
- **TP53:** Mutations in the TP53 gene, which codes for the p53 protein, lead to a loss of tumor suppressor function.
- **EGFR Amplification/Mutation:** Overexpression or mutations of the epidermal growth factor receptor (EGFR) lead to increased cell proliferation and survival.
- **IDH1/IDH2 Mutations:** Mutations in isocitrate dehydrogenase genes are less common in primary GBM but are associated with secondary GBM.
- **PTEN Loss:** Deletions or mutations in the PTEN gene result in uncontrolled cell growth due to the activation of the PI3K/AKT pathway.
2. **Signaling Pathways:**
- **RTK/PI3K/AKT/mTOR Pathway:** Dysregulation leads to increased proliferation, growth, and survival of tumor cells.
- **RAS/MAPK Pathway:** Aberrations contribute to cell growth and differentiation.
3. **Epigenetic Changes:**
- **MGMT Promoter Methylation:** Methylation of the MGMT gene promoter silences this DNA repair gene and influences response to alkylating agents like temozolomide.
- **Histone Modifications and miRNA Expression:** Changes in histone acetylation/methylation and miRNA profiles impact gene expression regulation.
4. **Tumor Microenvironment:**
- The microenvironment, including immune cells, blood vessels, and extracellular matrix, supports tumor growth and invasion.
- Hypoxia-inducible factors (HIFs) drive angiogenesis under low oxygen conditions.
Understanding these mechanisms provides insights into targeted therapies and treatment strategies for glioblastoma. - Treatment
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Treating glioblastoma is difficult due to several complicating factors:
The tumor cells are resistant to conventional therapies.
The brain is susceptible to damage from conventional therapy.
The brain has a limited capacity to repair itself.
Many drugs cannot cross the blood–brain barrier to act on the tumor.Treatment of primary brain tumors consists of palliative (symptomatic) care and therapies intended to improve survival. - Compassionate Use Treatment
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Glioblastoma, a highly aggressive type of brain cancer, has several avenues for experimental and off-label treatments under compassionate use. These treatments can include:
1. **Tumor Treating Fields (TTF):** This non-invasive treatment uses electric fields to disrupt cancer cell division.
2. **Immunotherapy:**
- **Checkpoint Inhibitors:** Drugs like pembrolizumab (Keytruda) are being tested to boost the body's immune response against tumor cells.
- **CAR-T Cell Therapy:** This involves reprogramming a patient's T-cells to target and kill cancer cells.
3. **Targeted Therapy:**
- **Bevacizumab (Avastin):** Although primarily used in other cancers, it's sometimes employed off-label to hinder the growth of blood vessels that supply the tumor.
- **Tyrosine Kinase Inhibitors:** Drugs targeting specific mutations within tumor cells are under investigation.
4. **Gene Therapy:** Techniques aiming to alter the genetic material within cancer cells to inhibit their growth are in experimental stages.
5. **Vaccines:** Experimental vaccines such as those targeting EGFRvIII, a specific mutation found in some glioblastoma cases, are being explored.
6. **Oncolytic Viruses:** These are modified viruses designed to infect and kill cancer cells specifically.
7. **Repurposed Drugs:** Certain existing drugs like the anti-parasitic agent mebendazole are being studied for their anti-cancer properties.
Patients considering these options should consult with their oncologist to evaluate the potential benefits, risks, and availability in clinical trials. - Lifestyle Recommendations
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Lifestyle recommendations for glioblastoma patients typically focus on improving overall well-being and supporting treatment:
1. **Nutrition**: Follow a balanced diet rich in fruits, vegetables, whole grains, and lean proteins to maintain strength and energy levels. Consider consulting a nutritionist specialized in cancer care.
2. **Exercise**: Engage in regular, moderate physical activity as tolerated to improve physical function and reduce fatigue. Always consult your healthcare provider before starting any exercise regimen.
3. **Rest**: Ensure adequate rest and sleep to help the body recover and manage treatment side effects.
4. **Stress Management**: Practice stress-reduction techniques such as meditation, yoga, or deep-breathing exercises to maintain mental and emotional health.
5. **Hydration**: Drink plenty of fluids to stay hydrated, particularly during treatment.
6. **Avoid Tobacco and Alcohol**: Refrain from smoking and limit alcohol consumption, as these can interfere with treatment and recovery.
7. **Follow Treatment Plans**: Adhere to prescribed treatments, medications, and follow-up appointments strictly.
8. **Support Systems**: Engage with support groups, counseling, or therapy to maintain emotional and psychological health.
9. **Safety Precautions**: Minimize fall risk and avoid activities that could lead to head injury, as patients with glioblastoma may experience seizures or motor deficits.
10. **Regular Monitoring**: Keep track of any new symptoms or changes in health and report them to your healthcare provider promptly. - Medication
- Glioblastoma is an aggressive form of brain cancer. Standard treatment usually involves a combination of surgery, radiation therapy, and chemotherapy. The most commonly used chemotherapy drug is temozolomide. In certain cases, the drug bevacizumab may be used to target tumor blood vessels. For recurrent glioblastoma, additional options such as lomustine may be considered.
- Repurposable Drugs
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Glioblastoma is a highly aggressive brain tumor with limited treatment options. Repurposable drugs being studied for glioblastoma include:
1. **Disulfiram** - Used for treating chronic alcoholism, it has shown potential to inhibit glioblastoma cell growth.
2. **Metformin** - Commonly used for Type 2 diabetes, it may inhibit tumor growth and enhance the effects of standard therapy.
3. **Itraconazole** - An antifungal, it may inhibit pathways involved in glioblastoma proliferation.
4. **Chloroquine/Hydroxychloroquine** - Known for treating malaria and autoimmune diseases, these drugs can inhibit autophagy, a process that tumors can exploit for survival.
5. **Valproic Acid** - Used for epilepsy and bipolar disorder, it has shown potential as an antitumor agent by modulating gene expression.
Research and clinical trials are ongoing to determine the efficacy and safety of these repurposable drugs for glioblastoma treatment. - Metabolites
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Glioblastoma, also known as glioblastoma multiforme (GBM), is a highly aggressive type of brain tumor. Metabolites are small molecules involved in metabolism. In the context of glioblastoma, certain metabolites have been found to be altered and can serve as biomarkers or therapeutic targets. For example:
1. **Lactate**: Increased levels due to the Warburg effect (aerobic glycolysis).
2. **2-Hydroxyglutarate (2-HG)**: Elevated in tumors with mutations in isocitrate dehydrogenase (IDH).
3. **Creatine**: Imbalances may indicate disrupted energy metabolism.
4. **Choline-containing compounds**: Elevated due to increased membrane turnover.
Nanotechnology (nan) applications in glioblastoma research include:
1. **Nanoparticles for Drug Delivery**: Enhancing the delivery of chemotherapy drugs to the tumor site while minimizing side effects.
2. **Nanosensors**: For early detection and monitoring of the tumor.
3. **Theranostics**: Combining therapeutic and diagnostic functions in a single nanodevice.
These advances aim to improve the effectiveness of glioblastoma treatment and diagnosis. - Nutraceuticals
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In the context of glioblastoma, nutraceuticals refer to food-derived products that may offer health benefits and support cancer treatment. Examples include curcumin, resveratrol, and green tea extract, which have shown some potential in preclinical studies for their anti-cancer properties. However, their effectiveness and safety in glioblastoma patients require more clinical research.
Nanotherapeutics involve the use of nanoparticles to deliver drugs directly to the tumor site, potentially improving the efficacy and reducing the side effects of treatments. In glioblastoma, nanotechnology is being explored to enhance the delivery of chemotherapy and targeted therapies across the blood-brain barrier, aiming for better treatment outcomes. These approaches are still largely experimental and under investigation in clinical trials. - Peptides
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Glioblastoma, a highly aggressive brain tumor, has been the focus of various advanced therapeutic strategies, including those involving peptides and nanotechnology:
1. **Peptides**: Peptides can be employed as targeted delivery agents or therapeutic agents due to their ability to bind specifically to tumor cells. This specificity can help in directly targeting glioblastoma cells, reducing damage to surrounding healthy tissues. Examples include peptide-based vaccines or ligands that can deliver drugs directly to tumor sites.
2. **Nanotechnology (Nanoparticles)**: Nanoparticles can be engineered to cross the blood-brain barrier and deliver drugs specifically to glioblastoma cells. These nanoparticles can be loaded with chemotherapeutic agents, RNAi molecules, or other therapeutic compounds, often coated with peptides or antibodies for targeting purposes. This approach aims to increase the efficacy of the treatment while minimizing side effects.
Both these strategies are being actively researched and hold promise for improving glioblastoma treatment outcomes.