Platinum Resistance in Ovarian Cancer

Ovarian cancer is the leading cause of death from gynecologic malignancy in the United Kingdom and the 4th most common cause of cancer mortality in women. Approximately 1 in 48 women in the UK will develop ovarian cancer in their lifetime. Surgery followed by chemotherapy involving a platinum-containing compound is the standard treatment for advanced disease. However, despite initial response rates of 70% to platinum-based chemotherapy, chemoresistance frequently develops and is in part responsible for the poor 5-year survival rate of just 30%. In this book, the role of the AKT pathway is examined in acquired platinum resistance using three isogenically matched cell line pairs derived from ovarian cancer patients, pre- and post-platinum resistant relapse. Findings here provide evidence for the role of DNA-PKcs in mediating the activation of AKT in response to DNA DSBs caused by the cytotoxic effects of cisplatin, which is observed in platinum-resistant ovarian cancer cell lines, but not platinum-sensitive cell lines. Targeting DNA-PKcs, in combination with platinum, presents a novel strategy of reversing platinum resistance and circumventing insulin-related toxicities.