Overcoming drug resistance in ovarian cancer through PI3K/AKT signaling inhibitors

Abstract

Ovarian cancer has been identified as the eighth most typical gynaecological malignancy and cause of health problems in women. For almost forty years, platinum doublet chemotherapy has usually been the cornerstone of first-line treatment regimens. The effectiveness of conventional chemotherapy is severely hampered by relapse rates and mortality from chemotherapy resistance, which lead to the spread and recurrence of malignant cancers as well as poor outcomes in terms of quality of life in patients.

Drug resistance has been linked to several mechanisms, including increased drug efflux, decreased apoptosis, increased autophagy, and changed drug metabolism. Further, the dysregulation of tumor suppressors or oncogenes plays a crucial role in chemoresistance. Additionally, PI3K/AKT/mTOR signaling has been implicated in several in vitro as well as clinical studies as a significant contributor to chemotherapy resistance in case of ovarian cancer. This review discusses the potential of various crude extracts, synthetic molecules, and nanoformulations for targeting PI3K/AKT/mTOR pathway. Moreover, a range of clinical studies involving PI3K/AKT/mTOR inhibitors have been summed up, addressing both the promises and complexities associated with their use. Overall, the review aims to provide a roadmap for future investigations that could lead to improved therapeutic outcomes for patients suffering from ovarian cancer, emphasizing the urgent need for continued exploration of novel pathways and strategies to combat drug resistance.