Noncoding RNAs in Therapeutic Resistance of Cancer

Despite the encouraging advances made to date in cancer therapy, the benefits to patients are frequently offset by the development of resistance to therapeutics. Given their involvement in regulating multiple aspects of gene expression and cell signaling that dictates the behaviors of malignant cells, it is not surprising that noncoding RNAs (ncRNAs) play pivotal roles in the resistance of cancers to clinically available therapeutics. Aberrant expression of these ncRNAs, attributed to inherent defects or stress-responsive variations, mediates cellular signaling that compensates for unfavorable molecular events elicited by the therapeutics, thereby preventing the pharmaceuticals from exerting their desired effects on their cellular targets; alternatively, ncRNAs may regulate cancer therapeutic sensitivity by affecting drug accessibility to neoplastic cells and in vivo drug metabolism. In addition, dysregulation of ncRNA expression in cancer stromal cells can impair the responsiveness of neoplastic cells to appropriate therapies. In this chapter, we will describe ncRNA-related mechanisms underlying cancer resistance to routine therapeutics, hopefully providing rationales for the development of drug-sensitizing strategies targeted against or based on these ncRNAs.