Integrating targeted drugs with taxanes and platinums: opportunities and challenges

In ovarian cancer, multiple attempts to adjust the standard taxane/platinum doublet by adding cytotoxic therapy or varying scheduling, dosage, and delivery have been met with limited success. Alternative methods to improve the grim prognosis of ovarian cancer, including molecular therapies, are currently under investigation. Efforts have been made to study tyrosine kinase inhibitors (including imatinib and pazopanib), Src kinase inhibitors and histone deacetylase inhibitors (HDACi) in combination with taxanes/platinums in order to improve efficacy. Unfortunately, while many pre-clinical and early phase clinical trials argue that the utilization of these molecular targets may enhance survival, only modest benefit has been seen in larger clinical trials. Other agents that have been evaluated include proteasome inhibitors, folate receptor antagonists, MEK inhibitors and opiate antagonists. In this review, we discuss the mechanisms of these targeted therapies and highlight the current and ongoing clinical trials that utilize these targeted agents in combination with taxanes and platinums in advanced ovarian cancer.