Mechanisms and Treatment Considerations of Chemotherapeutic Resistance within BRCA-Mutated Ovarian Cancer

Abstract

Ovarian cancer is the cause for the 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 or 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 arise through DNA repair by cancer cells, drug efflux for medication to be pumped 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 therapy, which uses the effects of two types of chemotherapies simultaneously, or drug holidays, where patients take breaks from treatment, increasing chemosensitivity. However, despite having found viable treatment approaches, medical professionals are researching 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.