Using GPCRs as Molecular Beacons to Target Ovarian Cancer with Nanomedicines

SIMPLE SUMMARY: The five-year survival rate for ovarian cancer is less than 50%, resulting in a global burden of >140,000 deaths annually. Late detection, cancer heterogeneity, and recurrent disease all contribute to treatment failure. Herein, recent advancements in the targeted delivery of therapeutics to ovarian cancer using nanoparticles are reviewed. In addition, we explore the applicability of targeting highly expressed cell surface receptors in ovarian cancer tissue to direct drug-loaded nanoparticle delivery systems. Targeted nanomedicine strategies have the potential to increase drug accumulation in tumor cells, prevent adverse effects on healthy tissue and lead to improved patient outcomes. ABSTRACT: The five-year survival rate for women with ovarian cancer is very poor despite radical cytoreductive surgery and chemotherapy. Although most patients initially respond to platinum-based chemotherapy, the majority experience recurrence and ultimately develop chemoresistance, resulting in fatal outcomes. The current administration of cytotoxic compounds is hampered by dose-limiting severe adverse effects. There is an unmet clinical need for targeted drug delivery systems that transport chemotherapeutics selectively to tumor cells while minimizing off-target toxicity. G protein-coupled receptors (GPCRs) are the largest family of membrane receptors, and many are overexpressed in solid tumors, including ovarian cancer. This review summarizes the progress in engineered nanoparticle research for drug delivery for ovarian cancer and discusses the potential use of GPCRs as molecular entry points to deliver anti-cancer compounds into ovarian cancer cells. A newly emerging treatment paradigm could be the personalized design of nanomedicines on a case-by-case basis.