ABCB1-Mediated Olaparib Resistance in Cervical Cancer: Molecular Mechanisms and Therapeutic Strategies.

Globally, cervical cancer is the fourth most common cancer among women and the second most common cancer in India after breast cancer, with the highest burden occurring in low- and middle-income countries. Although platinum-based chemotherapy and concurrent chemoradiotherapy improve outcomes in early-stage disease, multidrug resistance (MDR) remains a major cause of treatment failure in persistent, recurrent, and metastatic cervical cancer. Olaparib, a poly(ADP-ribose) polymerase inhibitor (PARPi), has emerged as a promising targeted therapeutic agent; however, it is not currently approved as a standard treatment for cervical cancer, and acquired resistance limits its long-term efficacy. One of the principal mechanisms underlying olaparib resistance is the overexpression of ATP-binding cassette subfamily B member 1 (ABCB1), also known as P-glycoprotein (P-gp), which actively exports olaparib from cancer cells, thereby reducing intracellular drug accumulation and therapeutic efficacy. Emerging evidence indicates that ABCB1-mediated resistance is regulated by gene amplification, dysregulated signaling pathways, epigenetic modifications, microRNA-mediated regulation, and human papillomavirus (HPV)-associated oncogenic signaling. This review summarizes the molecular mechanisms underlying ABCB1-mediated olaparib resistance in cervical cancer and highlights current and emerging therapeutic strategies, including selective ABCB1 inhibitors, natural phytochemicals, alternative PARP inhibitors with reduced P-glycoprotein-mediated efflux, nanotechnology-based drug delivery systems, receptor-targeted nanocarriers, co-delivery approaches, and gene-silencing technologies. These strategies may overcome multidrug resistance, enhance the therapeutic efficacy of olaparib, and support the development of personalized treatment approaches for cervical cancer.