Cancer drug resistance leading to therapeutic failure in the treatment of many cancers
encompasses various mechanisms and may be intrinsic relying on the patient’s genetic
makeup or be acquired by tumors that are initially sensitive to cancer drugs. All
in all, it may be responsible for treatment failure in over 90 % of patients with
metastatic cancer. Cancer drug resistance, in particular acquired resistance, may
stem from the micro-clonality/micro-genetic heterogeneity of the tumors whereby, among
others, the following mechanisms may entail resistance: altered expression of drug
influx/efflux transporters in the tumor cells mediating lower drug uptake and/or greater
efflux of the drug; altered role of DNA repair and impairment of apoptosis; role of
epigenomics/epistasis by methylation, acetylation, and altered levels of microRNAs
leading to alterations in upstream or downstream effectors; mutation of drug targets
in targeted therapy and alterations in the cell cycle and checkpoints; and tumor microenvironment
that are briefly reviewed.
