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Targeted Therapy: An Ongoing Journey to Tackle Brain Metastases

Author: Christine Chen

Editors: Rachel Chen

Artist: Leo Li

Brain cancer remains a challenge in the field of oncology. Many forms of therapy, including radiation therapy and chemotherapy, are limited in their efficiency and often cause negative side effects. However, over the last decade, targeted therapy—using drugs or antibodies to target proteins that control cancer growth—has become a promising treatment method for brain cancer. Targeted therapy is often used alongside chemotherapy, resulting in more efficient treatment and minimizing damage to normal tissues, a side effect of chemotherapy.

Brain metastases, the most common type of intracranial tumors, affect 20-40% of cancer patients. They occur when cancer cells spread from other parts of the body, such as the lungs, breasts, skin, or colon, to the brain. It often results in actionable mutations, which are DNA alterations affecting a patient's response to treatments like stereotactic radiosurgery, surgery, and whole-brain radiation therapy. This makes them ideal candidates for testing targeted therapy. While chemotherapy is generally ineffective due to the blood-brain barrier (BBB), some drugs have recently been discovered that can cross the BBB, suggesting that a combined treatment of chemotherapy and targeted therapy may be effective. The approach, as stated in the abstract of ‘Targeted Therapy of brain metastases: latest evidence and clinical implications,’ involves surgery, radiation, immunotherapy, and targeted therapy, leading to better control over the disease and a longer span of survival. The article discusses current methods of targeted therapy and their role in treating brain metastases originating from common tumors, such as non-small cell lung cancer (NSCLC), breast cancer, melanoma, and renal cell carcinoma.

Many existing studies focus on the treatment of metastases from NSCLC, as lung cancer causes the most cancer-related deaths, and 13-44% of patients develop brain metastases. NSCLC has many types, with adenocarcinoma being the most common. Targeted therapy, as suggested by its name, focuses on specific mutations, such as the epidermal growth factor receptor (EGFR). Suggested drugs include erlotinib and gefitinib, which show potential in treating brain metastases from NSCLC with EGFR mutations. Another drug, osimertinib, is approved for specific EGFR mutations. Aside from these larger mutations, around 3-7% of cases involve the fusion of two genes, ALK and EML4, effectively treated using crizotinib, ceritinib, alectinib, and brigatinib. Although numerous studies have revealed a positive impact on brain metastases with these drugs, more research is needed to understand the effectiveness of targeted approaches for lung cancer patients with other gene mutations.

Targeted treatments have been crucial in controlling cancer and extending patient survival. While there is still more to learn about the treatment’s efficacy and safety, especially since brain metastases start from somewhere else in the body, new drugs show promise in crossing the BBB. Further work is needed to determine the optimal drug dosage for effectiveness and to pass through the BBB. Many studies consider targeted therapy as a last resort, which is the ideal scenario. However, researchers and doctors face many challenges when studying the effectiveness of treatments for brain tumors.

 

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