Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises

SIMPLE SUMMARY: Ovarian cancer is the most lethal gynecological cancer. Currently there is no curative treatment for relapsed, standard treatment resistant ovarian cancer. Here we discuss and summarize recent clinical and preclinical studies concerning the possibility to use small molecule kinase inhibitors as a treatment of advanced platinum and taxane resistant ovarian cancer, with a focus on high grade serous ovarian cancer, the most common and most aggressive form of it. Some of these results seem rather promising and support for the feasibility of kinase inhibition as a personalized combinatory treatment. This will optimally require tumor sequencing, longitudinal sampling, and additional preclinical and clinical studies. ABSTRACT: Ovarian cancer is the deadliest gynecological cancer, the high-grade serous ovarian carcinoma (HGSC) being its most common and most aggressive form. Despite the latest therapeutical advancements following the introduction of vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors and poly-ADP-ribose-polymerase (PARP) inhibitors to supplement the standard platinum- and taxane-based chemotherapy, the expected overall survival of HGSC patients has not improved significantly from the five-year rate of 42%. This calls for the development and testing of more efficient treatment options. Many oncogenic kinase-signaling pathways are dysregulated in HGSC. Since small-molecule kinase inhibitors have revolutionized the treatment of many solid cancers due to the generality of the increased activation of protein kinases in carcinomas, it is reasonable to evaluate their potential against HGSC. Here, we present the latest concluded and on-going clinical trials on kinase inhibitors in HGSC, as well as the recent work concerning ovarian cancer patient organoids and xenograft models. We discuss the potential of kinase inhibitors as personalized treatments, which would require comprehensive assessment of the biological mechanisms underlying tumor spread and chemoresistance in individual patients, and their connection to tumor genome and transcriptome to establish identifiable subgroups of patients who are most likely to benefit from a given therapy.