Clinical trials and future potential of targeted therapy for ovarian cancer

Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage with a poor prognosis. Currently, surgical tumor debulking followed by chemotherapy based on platinum and taxane is the standard treatment for advanced disease. However, these patients remain at great risk for recurrence and developing drug resistance. Therefore, new treatment strategies are needed to improve outcomes for patients with advanced and recurrent ovarian cancer. Several agents targeted at particular molecules have been developed for ovarian cancer and are now entering clinical trials. The functional targets of these agents are aberrations in tumor tissues including angiogenesis, the human epidermal growth factor receptor family, poly(ADP-ribose) polymerase (PARP), mammalian target of rapamycin (mTOR) signaling pathway, and alpha-folate receptor (alpha-FR). The anti-angiogenic compound bevacizumab has been reported as the most effective targeted agent. Bevacizumab plus chemotherapy prolonged progression-free survival (PFS) both for advanced and platinum-sensitive recurrent ovarian cancer, but did not increase overall survival. A PARP inhibitor, olaparib, applied as maintenance treatment also improved PFS in platinum-sensitive relapsed ovarian cancer. Furthermore, mTOR inhibitors and a monoclonal antibody to alpha-FR, farletuzumab, are attractive treatment strategies either alone or combined with chemotherapy. Understanding the tumor molecular biology and identifying predictive biomarkers are essential steps in selecting the best treatment strategies. This article reviews available clinical data on the most promising targeted agents for ovarian cancer.