Patient-derived tumor models are attractive tools to repurpose drugs for ovarian cancer treatment: pre-clinical updates

Abstract

Despite advances in understanding of ovarian cancer biology, the progress in translation of research findings into new therapies is still slow. It is associated in part with limitations of commonly used cancer models such as cell lines and genetically engineered mouse models that lack proper representation of diversity and complexity of actual human tumors. In addition, the development of de novo anticancer drugs is a lengthy and expensive process. A promising alternative to new drug development is repurposing existing FDA-approved drugs without primary oncological purpose. These approved agents have known pharmacokinetics, pharmacodynamics, and toxicology and could be approved as anticancer drugs quicker and at lower cost. To successfully translate repurposed drugs to clinical application, an intermediate step of pre-clinical animal studies is required. To address challenges associated with reliability of tumor models for pre-clinical studies, there has been an increase in development of patient-derived xenografts (PDXs), which retain key characteristics of the original patient's tumor, including histologic, biologic, and genetic features. The expansion and utilization of clinically and molecularly annotated PDX models derived from different ovarian cancer subtypes could substantially aid development of new therapies or rapid approval of repurposed drugs to improve treatment options for ovarian cancer patients.

Keywords: PDX; ovarian cancer; repurposed drugs; tumor models.