Drug resistance in cancer: mechanisms and tackling strategies

Abstract

Drug resistance developed towards conventional therapy is one of the important reasons for chemotherapy failure in cancer. The various underlying mechanism for drug resistance development in tumor includes tumor heterogeneity, some cellular levels changes, genetic factors, and others novel mechanisms which have been highlighted in the past few years. In the present scenario, researchers have to focus on these novel mechanisms and their tackling strategies. The small molecules, peptides, and nanotherapeutics have emerged to overcome the drug resistance in cancer. The drug delivery systems with targeting moiety enhance the site-specificity, receptor-mediated endocytosis, and increase the drug concentration inside the cells, thus minimizing drug resistance and improve their therapeutic efficacy. These therapeutic approaches work by modulating the different pathways responsible for drug resistance. This review focuses on the different mechanisms of drug resistance and the recent advancements in therapeutic approaches to improve the sensitivity and effectiveness of chemotherapeutics.

Keywords: Cancer; Drug efflux; Drug resistance; Epigenetics; Membrane lipids; Multidrug resistance; Nanochemotherapeutic; Prodrug; Tumor microenvironment.