Targeted molecular therapies for ovarian cancer: An update and future perspectives (Review)

Abstract

Abstract. Identification of the potential gene expression profiles of epithelial ovarian cancer and the arrival of newly targeted therapies have advanced the strategies used for treatment of this disease. This review focuses on the design of ongoing and planned clinical trials and offers a synopsis of the Englishlanguage literature for preclinical and clinical targeted therapies for epithelial ovarian cancer. Among many targeted agents, a promising, novel class of targeted drugs for special patient populations expected to improve the effectiveness of current therapy include inhibitors of angiogenesis, poly (ADP ribose) polymerase (PARP) and DNA repair mechanisms. Inhibition of PARP or homologous recombination (HR) repair mediated by Chk1 (checkpoint kinase 1) would selectively sensitize p53 mutation, BRCAness phenotype (serous type ovarian cancer) or HNF (hepatocyte nuclear factor)-1β-overexpressing tumor cells (clear cell type ovarian cancer) to chemotherapeutic agents. The therapeutic response is likely to be limited to a targeted patient, but not to the broad population. This review discusses some of the key current developments and existing challenges.

Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53

“…Most patients will have appropriate surgical staging followed by optimal surgical cytoreduction, with the goal being to remove all gross disease before starting chemotherapy (2). There are a number of important issues to be resolved in the management of ovarian cancer that relates to surgery, including the role of surgical interval cytoreduction, as well as the role of second-look laparotomy (3). There are basically three initial chemotherapy options considered the standard of care at the present time for the treatment of ovarian cancer.…”

“…While ovarian cancer has a typically good response to first-line combination chemotherapy after initial cytoreductive surgery, the prognosis of patients with advanced malignant ovarian cancer remains poor because of acquired chemotherapy resistance (2). Despite recent advances made in chemotherapies of ovarian cancer, the overall survival of patients has not improved significantly because a considerable number of patients harbor ovarian cancer refractory to these therapies and the majority of the initially responsive tumors become resistant to treatments (3). Thus, the development of novel targeted therapy that retains activity against chemotherapy-resistant ovarian cancer is an unmet and urgent medical need.…”

Essential role of autophagy in fucoxanthin-induced cytotoxicity to human epithelial cervical cancer HeLa cells

“…Treatment success of recurrent ovarian cancer is limited by the emergence of chemoresistance. Chemoresistance commonly results from dysregulation of the apoptotic pathway [1] . Therefore, agents that are identified to exert a novel cell death mode may have the potential to be effective against chemoresistant diseases.…”

Attenuation of MUC4 potentiates the anticancer activity of auranofin via regulation of the Her2/Akt/FOXO3 pathway in ovarian cancer cells

“…Although ovarian cancer after initial cytoreductive surgery has been generally shown to have a favorable response to combination chemotherapy (first line), advanced ovarian cancer is responsible for the worse prognosis of patients, due to acquired chemotherapy resistance (24,25). While chemotherapies for ovarian cancer are currently being developed, the overall survival has not considerately increased since a significant number of these patients develop a resistance to the therapies and the majority of cancers susceptible to treatments in the beginning, become refractory (26). Therefore, a new targeted therapy needs to be developed for ovarian cancer resistance to chemotherapy.…”