Overview of BH3 mimetics in ovarian cancer

Ovarian carcinoma is the leading cause of gynecological cancer-related death with still a five-year dismal prognosis, mainly due to the late diagnosis and the emergency of resistance to both cytotoxic and targeted agents. Bcl-2-family proteins have a key role in apoptosis and have been shown to be associated with tumor development/progression and response to therapy in different tumor type, including ovarian carcinoma. In tumors, evasion of apoptosis through down-regulation of pro-apoptotic and/or up-regulation of anti-apoptotic proteins is a possible mechanism of resistance to therapy. BH3 mimetics are small molecules that occupy the hydrophobic pocket on pro-survival proteins, allowing the induction of apoptosis and are currently under study as single agents and/or in combination with both cytotoxic and targeted agents in oncology. We will, here, discuss and review the recent advancements in targeting anti-apoptotic protein of Bcl-2 family for ovarian cancer treatment, focusing on BH3 mimetics, and how these approaches could potentially represent an alternative/complementary approach to treat patients and to overcome/delay resistance to current treatments.