Boosting bioavailability of PROTACs for ovarian cancer: From chemistry to clinical translation

Ovarian cancer is a significant clinical problem with late diagnosis, high recurrence, and resistance to therapy. Greater reliance on ubiquitin to induce the degradation of oncogenic proteins instead of inhibiting their activity is provided by proteolysis-targeting chimeras (PROTACs). This review outlines the molecular architecture of PROTACs, their use against important ovarian cancer-driven molecular targets, including BRD4, NAMPT, FAK, FER, and TG2, and the benefits over traditional inhibitors, which include enhanced selectivity, longer efficacy, and ability to target undruggable targets. We also talk about the key obstacles to clinical translation, such as off-target effects, unfavorable pharmacokinetics, and tumor microenvironment concerns, and emerging technologies, including nanoparticle delivery and light-responsive or reversible PROTACs. As PROTACs progress from preclinical research to clinical implementation, their incorporation into ovarian cancer treatment presents a new model for precision oncology. This review highlights the therapeutic potential of PROTACs by linking preclinical progress to translational options to expand precision oncology to treat ovarian cancer.