Facing Challenges in Brain Cancer Treatment
Facing Challenges in Brain Cancer Treatment
Treating glioblastoma multiforme (GBM), a particularly challenging form of brain cancer, presents numerous obstacles.
GBM treatment is fraught with difficulties due to the tumor’s deep-seated location within the brain and its protection by the blood-brain barrier. This barrier impedes the effective delivery of chemotherapy drugs to the tumor site. Additionally, the indistinct margins of the tumor make complete surgical resection challenging. Clinical evidence suggests that maximal tumor resection significantly improves patient survival.
Moreover, residual tumor cells and cancer stem cells may continue to proliferate, leading to an increased rate of GBM recurrence. The regenerative microenvironment following tumor resection further enhances the malignancy of remaining brain cancer cells, while tumor heterogeneity limits the efficacy of single-target therapies. Cancer stem cells, rapid proliferation, and recurrence contribute to disease progression. Furthermore, chemotherapy resistance and immune suppression undermine conventional treatments, including chemotherapy and immunotherapy, while current chemotherapy drugs often induce neurological side effects and increase the burden on caregivers. These factors collectively pose significant challenges to the prognosis of brain cancer patients.
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Background of GBM
- Lack of effective treatment: According to statistics from the American Cancer Society (ACS) and the Central Brain Tumor Registry of the United States (CBTRUS), an estimated 20,000 new brain tumor cases are diagnosed each year, with approximately 400 new cases of malignant gliomas in Taiwan annually. The current conventional therapies for treating malignant brain tumors, including surgical treatment, radiation therapy, and chemotherapy, have very limited efficacy. Furthermore, due to the protection of the blood-brain barrier in the affected area, there are currently no truly curative drugs available, necessitating the development of new-generation therapies.
- Rapid recurrence and low survival rates: Glioblastoma Multiforme (GBM) can grow up to 16 times its size within one month and is a rapidly worsening primary brain tumor. The recurrence rate after surgery is also very high, often requiring patients to repeatedly undergo hospital treatments. Patients diagnosed with stage IV GBM have an average survival time of only 12 to 18 months. Malignant brain tumors spread rapidly and are challenging to eradicate. Once diagnosed, they are usually in advanced stages, and the average survival period is often around one year, with a 5-year survival rate of only 3.4%. The current standard treatment for malignant brain tumors involves a combination of surgery, radiation therapy, and chemotherapy, all of which have limited effectiveness.
- Several celebrities have encountered this unfortunate condition: Prominent individuals both domestically and internationally have died from incurable GBM, including U.S. Senators John Sidney McCain and Edward M. Kennedy, British politician Tessa Jowell, and New York Times journalist Tom Wicker.
- Diagnosis: The most common early symptom of brain tumors is headaches. Clinical symptoms may include headaches, increased intracranial pressure, double vision, and difficulty articulating thoughts, all of which may indicate a possible brain tumor. These symptoms are usually due to the tumor’s growth causing compression and edema in the brain tissues. Therefore, it is essential to be vigilant about any unusual bodily changes. If the above symptoms occur and worsen progressively, they may be related to GBM, making early detection challenging. In 2018, a woman named Mrs. Guo from Tzu Chi Hospital was diagnosed with GBM after experiencing sudden paralysis and collapsing due to dizziness.
Challenges in Brain Cancer Treatment
Brain Tumor Location
- Protected by the Scalp and Skull: Malignant brain tumors are typically located in areas that even the most skilled neurosurgeons cannot access without penetrating the scalp and skull during surgery.
- Ill-defined Margins – Difficult to Completely Remove Tumors: The indistinct margins of tumors make it challenging for neurosurgeons to achieve complete resection. Additionally, tumors may be located close to brain regions with similar physiological functions, further complicating the task of maximizing tumor removal, posing a significant challenge for physicians.
Blood-brain barrier
- The Blood-Brain Barrier (BBB) is a highly specialized barrier that separates the bloodstream from the central nervous system (CNS), consisting of the brain’s blood vessels and the CNS. Composed of specialized endothelial cells that cover the brain capillaries, the BBB regulates the passage of substances between the bloodstream and the brain. Its structure and function depend on complex interactions between different cell types, such as endothelial cells, astrocytes, and pericytes, as well as the extracellular matrix in the capillaries. These cells are tightly arranged, preventing most substances from entering the brain tissue. The BBB’s role is to protect the brain from toxins, bacteria, viruses, and other harmful substances present in the blood, while also regulating the transport of essential molecules and maintaining a stable environment. However, this barrier also poses a challenge in treating diseases of the CNS, as it restricts the passage of therapeutic agents, including chemotherapy drugs, to the site of the disease. Therefore, overcoming the BBB is a significant challenge in brain cancer treatment.
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Tumor Heterogeneity
- Tumor heterogeneity refers to differences observed among individual cells within a tumor, which directly impact prognosis and treatment response. In addition to intratumor heterogeneity, which pertains to differences among cells within a single tumor, there is also intertumor heterogeneity, which refers to differences observed at the population level. Tailoring the most effective treatment to different subpopulations can help personalize treatment plans for GBM patients.
Tumor Microenvironment
Cancer Stem Cells – Rapid Proliferation and Recurrence: Residual brain tumor cells contain a small number of cancer stem cells, which continuously divide and generate other tumor cells that do not possess stem cell properties, leading to tumor recurrence.
Chemotherapy Drug Resistance: Prolonged use of the current first-line chemotherapy drug, Temozolomide, leads to the production of O6-methylguanine methyltransferase (MGMT) in glioblastoma cells. MGMT repairs DNA damage caused by Temozolomide, rendering the tumor resistant to chemotherapy drugs and thus unable to effectively kill cancer cells.
Immune Suppression: Brain tumor cells achieve immune suppression by modulating the tumor microenvironment. This includes producing various immune-suppressive proteins or inhibiting antigen-presenting cells and attracting more immune-suppressive cells into the brain tumor microenvironment. This immune escape phenomenon accelerates disease progression.
Poor Quality of Life
Patients undergoing brain cancer treatment often experience post-operative wound complications, pain, seizures, and edema. Additionally, the administration of chemotherapy drugs often leads to neurological side effects, further deteriorating the patients’ quality of life and increasing the burden on their caregivers.
Why Target Glioblastoma Multiforme (GBM)
There have been no new advancements in Glioblastoma Multiforme (GBM) treatment for nearly 20 years, compared to other cancer treatments such as lung cancer, where over 30 drugs have been introduced in the past two decades.
This highlights the difficulties and challenges faced globally in the treatment of brain cancer, which is a primary reason for our active involvement in this field.
Cerebraca® Wafer is designed to overcome key challenges in the treatment of Glioblastoma Multiforme (GBM), providing a solid foundation for superior clinical outcomes
One key aspect of Cerebraca® Wafer is its ability to eradicate residual tumor cells and suppress cancer stem cells after brain surgery. Implanted at the surgical resection site, Cerebraca® Wafer creates a local environment with high drug concentration, excellent penetration, and sustained release for 30 days to inhibit the growth of remaining tumor cells.
Following tumor resection, the regenerative microenvironment further enhances the malignancy of residual GBM cells. Tumor heterogeneity limits the effectiveness of single-targeted therapy. Cancer stem cells, rapid proliferation, and recurrence contribute to disease progression. Additionally, chemotherapy drug resistance and immune suppression lead to the failure of conventional treatments, including chemotherapy and immunotherapy. To address these multifaceted challenges, the active ingredient EF-API-001 in Cerebraca® Wafer is a multifunctional drug that targets cancer stem cells, reduces chemotherapy drug resistance, and activates the immune system. Unlike currently available treatments, which often result in neurological side effects and increased caregiver burden, clinical trial results with Cerebraca® Wafer show that the treatment does not cause additional adverse events, thus improving quality of life post-treatment.
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