Cisplatin Resistance in Cancer Therapy: Causes and Overcoming Strategies

Dr. S. Shruthi, Prof. Dr. K. Bhasker Shenoy. Cisplatin (CDDP) is the first metal-based drug and has been a popular drug in the treatment of various types of cancer for decades. Cancer cell death is promoted by this platinum-based drug by generating DNA adducts and activating apoptotic signaling pathways. The development of drug resistance is the foremost clinical concern that compromises its efficacy. The mechanism of CDDP resistance encompasses changes in drug influx and efflux, drug accumulation reduction, enhanced drug detoxification, and repair which may affect its therapeutic value. Researchers have paid significant attention to overcoming CDDP resistance, which provides an opportunity to enhance clinical outcomes. Combinational therapy, use of CDDP analogs, phytochemicals, nanoparticle-mediated drug delivery, gene targeting and regulation of drug induced epigenetic changes are the specific regimens to overcome CDDP resistance and treatment burden. In this review, we summarize the mechanisms involved in CDDP resistance and strategies considered to overcome these hurdles concerning preclinical and clinical studies. This may provide insights into the further development of novel approaches to uproot CDDP resistance, to ascertain a safer and more effective cancer therapy. Cisplatin (CDDP) resistance, a major hurdle in cancer treatment, arises from various mechanisms, including reduced drug uptake, increased drug efflux, enhanced DNA repair, and altered apoptotic pathways. Overcoming this challenge requires a multifaceted approach. Combination therapies, such as treating CDDP with other chemotherapeutic agents or targeted therapies, can circumvent resistance by targeting alternative pathways. Additionally, novel drug delivery systems, like nanoparticles or liposomes, can improve drug accumulation within cancer cells, overcoming resistance associated with decreased drug uptake. By integrating these approaches, researchers aim to enhance the efficacy of CDDP-based therapies and improve outcomes for cancer patients. image