Ovarian cancer: Targeted therapies and mechanisms of resistance

Abstract Ovarian cancer is one of the leading causes of cancer-related mortality in women. The treatment of ovarian cancer consists of surgical removal of vast majority of the tumor mass followed by chemotherapy, hormone therapy, and/or radiotherapy of the remaining mass and metastases. A variety of chemotherapeutic drugs have been used in gynecologic cancers either alone or in combination therapy such as cisplatin, carboplatin, paclitaxel, docetaxel, doxorubicin, cyclophosphamide, gemcitabine, topotecan, and vinorelbine. Even though the combination therapy has a 70% response rate, tumor relapse and subsequent chemoresistance are frequently observed, eventually resulting in treatment failure and mortality in majority of the patients. Chemoresistance can be intrinsic or acquired through various cellular modifications, and drugs targeting these systems can overcome the chemoresistance and hopefully extend patient survival. Targeted therapy is a relatively new treatment approach where the drugs attack the oncogenic pathways in the malignant cells. Targeted therapy is designed to selectively target the molecules and mechanisms that cause chemoresistance and eliminate them so that chemotherapeutic drugs can work to their full potential of antitumor activity. Since these pathways are associated with chemoresistance, targeting them could help sensitize the malignant cells to standard chemotherapy drugs. Some of the drugs include efflux pump inhibitor, tariquidar, tyrosine kinase inhibitors such as erlotinib and gefitinib, and PARP inhibitors such as olaparib, veliparib, and p53 inhibitors. This research chapter discusses in detail about the current targets and related drugs for better management of patients with ovarian cancer and improved quality of life.