Modification of Drug Response in Cancer by MicroRNAs

Especially in chemoresistant cancers, such as lung and pancreatic cancer, there is a clear need to understand molecular mechanisms behind drug resistance and develop effective therapies. Resistance can be caused by a range of mechanisms, including modulation by microRNAs (miRNAs). miRNAs are involved in many biological processes and have been implicated in cancer initiation and progression. However, they can also alter cellular response to anticancer agents by modulating survival pathways, apoptosis and DNA repair systems. One of the major features of miRNAs is their ability to target multiple genes and therefore interfere in multiple pathways. This explains their role in multiple pathways involved in resistance and makes them attractive as novel class of therapeutic targets. Here, we describe the molecular basis of miRNAs in anticancer drug resistance, including alterations in cell survival and apoptosis, as well as drug targets. The possibility to modulate miRNA expression to enhance drug sensitivity and the development of miRNA-based therapeutics as novel drugs is discussed. The implications are illustrated with a clinical focus on the application of miRNAs in pancreatic cancer and lung cancer, for which resistance to current therapies remains a major problem.