Emerging serine-threonine kinase inhibitors for treating ovarian cancer

Introduction: Ovarian cancer is the leading cause of gynecologic cancer death, owing to high rates of incurable, recurrent disease after initial treatment. Serine threonine kinases (STKs) have been proposed as potential therapeutic targets in ovarian cancer because of their role in the initiation and progression of cancers. Experience in non-ovarian cancers suggests that STK inhibitors are active against tumors with specific molecular alterations. Areas covered: This review discusses STK inhibitors in active development in phase II/III clinical trials for ovarian cancer. PubMed and ClinicalTrials.gov were systematically searched to identify STK inhibitor trials for ovarian cancer; active development was confirmed via Pharmaprojects. Available data regarding the efficacy and safety of these compounds are explored. Expert opinion: STK inhibitors currently in development have modest activity as single agents and are unlikely to achieve approval as monotherapy for unselected ovarian cancer patients. Combination trials of STK inhibitors with chemotherapy and/or targeted therapies have suggested an acceptable efficacy/toxicity ratio for certain combinations but confirmatory studies are needed. Carefully designed trials, especially those including somatic molecular analysis, may help identify the subsets of patients most likely to benefit from these therapeutic strategies and determine the role of STK inhibitors in the evolving landscape of precision oncology.