title: Molecular mechanisms underlying the role of microRNAs (miRNAs) in anticancer drug resistance and implications for clinical practice.
abstract: Drug resistance remains a major problem in the treatment of cancer patients for both conventional chemotherapeutic and novel biological agents. Intrinsic or acquired resistance can be caused by a range of mechanisms, including increased drug elimination, decreased drug uptake, drug inactivation and alterations of drug targets. Recent data showed that other than by genetic (mutation, amplification) and epigenetic (DNA hypermethylation, histone post-translational modification) changes, drug resistance mechanisms might also be regulated by microRNAs (miRNAs). In this review we provide an overview on the role of miRNAs in anticancer drug resistance, reporting the main studies on alterations in cell survival and/or apoptosis pathways, as well as in drug targets and determinants of drug metabolism, mediated by deregulation of miRNA expression. The current status of pharmacogenetic studies on miRNA and their possible role in cancer stem cell drug resistance are also discussed. Finally, we integrated the preclinical data with clinical evidences, in lung and pancreatic cancers, showing how the study of miRNAs could help to predict resistance of individual tumours to different anticancer drugs, and guide the oncologists in the selection of rationally based tailor-made treatments.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. elisa.giovannetti@gmail.com
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.forename: Ayse
authors.initials: A
authors.lastname: Erozenci
authors.forename: Jorn
authors.initials: J
authors.lastname: Smit
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs