Tumour microenvironment and aberrant signaling pathways in cisplatin resistance and strategies to overcome in oral cancer

Objective: Oral cancer is the sixteenth most prevalent cancer in the world and the third-most in India. Despite of several treatment modalities, the cure rate of oral cancer is still low due to drug resistance mechanisms, which are caused by many reasons. It is necessary to improve the existing treatment strategies and discover neoteric therapy to kill cancer cells, which will give oral cancer's cure rate more success. So this review aims to delineate the molecular mechanisms behind cisplatin resistance, specifically the role of the tumor microenvironment, extracellular vesicles, and altered signaling pathways and its overcoming strategies in oral cancer. Design: This review was designed by searching words like cancer, oral cancer, cisplatin-resistance, tumor microenvironment, aberrant signalings, and extracellular vesicles, overcoming strategies for cisplatin resistance in databases like PubMed, Google Scholar, web science, and Scopus. Data available in this review is from 2017 to 2021.Results: After searching too much data, we found these 98 data appropriate for our review. From these data, we found that tumor microenvironment, extracellular vesicles, and altered signaling pathways like PI3K/AKT, EGFR, NOTCH, Ras, PTEN, Nf-kappa beta, and Wnt signaling have a crucial role in resistance development towards cisplatin in oral cancer.Conclusions: Lastly, this review explores the alternative strategies to overcome cisplatin resistance likely, the combination therapy and targeted therapy by combining more than one chemotherapeutic drug or inhibitors of signaling pathways and also by using nanoparticle loaded drugs that will reduce the drug efflux, which gives new treatment strategies.