Priyal Tyagi

How does BRCA1/BRCA2 mutation lead to chemotherapeutic resistance in hereditary breast and ovarian cancer?

Started June 4, 2023

Abstract or project description

Ovarian cancer is the cause for most gynecological cancer deaths and can develop through hereditary syndromes such as Hereditary Breast and Ovarian Cancer syndrome (HBOC). Ovarian cancer developed by this hereditary syndrome occurs when an individual has mutations in tumor suppressor genes BRCA1 and BRCA2, resulting in cancers such as breast and ovarian cancer. While it is often treated with chemotherapies such as cisplatin (platinum-based chemotherapy), many patients develop chemoresistance to first line therapies. Chemoresistance can occur through DNA repair by cancer cells, drug efflux to pump medication out of the cell, and autophagy to recycle damaged organelles for energy. Following chemoresistance, patients must be treated with a second-line therapy such as combination therapies, which use the effects of two types of chemotherapies simultaneously, or drug holidays, where patients take breaks from treatment, increasing chemosensitivity. However, despite treatment approaches, medical professionals are finding methods of preventing chemoresistance. Monitoring the growth of cancer through biomarkers can help alert doctors to development of chemoresistance. In addition, combination therapy can be administered as a first-line therapy in order to prevent the onset of chemoresistance. By studying mechanisms of chemoresistance, effective treatment options and prevention methods can be used to benefit patients with ovarian cancer.