Hereditary ovarian cancer. The role of BRCA1 gene dysfunction in response to chemotherapy

Abstract

Summary Hereditary ovarian cancer is often believed to be as a distinct disease. It is diagnosed earlier than its sporadic type; serous subtypes and more advanced stages are usually observed. Mutations of genes like BRCA1, BRCA2, MMR (MLH1, MSH2, PMS1, PMS2) are strictly associated with the heredity of ovarian and also breast cancer. Systematic controls and specific procedures to lower the risk of those tumors are required for mutation carriers. Most authors emphasize better prognosis for patients with inherited type of ovarian cancer when comparing to sporadic one. It probably results from dysfunction of BRCA1 gene, inducing better response to platinum-based cytostatic drugs. This phenomenon, called “BRCAness profile”, is also observed in non-hereditary ovarian cancers and it arises from somatic mutation or hypermetylation of BRCA1 promoter. Thus, the process of DNA repair is defective. Currently new groups of drugs using the BRCA1 dysfunctions are being introduced into clinical practice.