Cancer Chemoresistance; Recent Challenges and Future Considerations.

Abstract

Cancer remains one of the serious health hazards and major causes of human mortality across the world. Despite the development of many typical antineoplastic drugs and introduction of novel targeted agents, chemoresistance constitutes a major challenge in the effective therapeutic management of cancer. Drug inactivation, efflux of anticancer agents, modification of target sites, enhanced repair of DNA damage, apoptosis failure and induction of epithelial-mesenchymal transition are the principal mechanisms of cancer chemoresistance. Moreover, epigenetics, cell signaling, tumor heterogeneity, stem cells, microRNAs, endoplasmic reticulum, tumor microenvironment and exosomes have also been implicated in the multifaceted phenomenon of anticancer drug resistance. The tendency of resistance is either intrinsically possessed or subsequently acquired by cancerous cells. From clinical oncology standpoint, therapeutic failure and tumor progression are the most probable consequences of cancer chemoresistance. Combination therapy can help to overcome the issue of drug resistance, and therefore, the development of such treatment regimens is recommended for counteracting the emergence and dissemination of cancer chemoresistance. This chapter outlines the current knowledge on underlying mechanisms, contributory biological factors and likely consequences of cancer chemoresistance. Besides, prognostic biomarkers, diagnostic methods and potential approaches to overcome the emergence of antineoplastic drug resistance have also been described.