Critical Reviews in Oncology / Hematology
Volume 81, Issue 2 , Pages 103-122, February 2012

Molecular mechanisms underlying the role of microRNAs (miRNAs) in anticancer drug resistance and implications for clinical practice

  • Elisa Giovannetti

      Affiliations

    • VU University Medical Center, Amsterdam, The Netherlands
    • Department Internal Medicine, University of Pisa, Pisa, Italy
    • Corresponding Author InformationCorresponding author at: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Tel.: +31 20 4442267; fax: +31 20 4443844.
    • ,
  • Ayse Erozenci

      Affiliations

    • VU University Medical Center, Amsterdam, The Netherlands
    • ,
  • Jorn Smit

      Affiliations

    • VU University Medical Center, Amsterdam, The Netherlands
    • ,
  • Romano Danesi

      Affiliations

    • Department Internal Medicine, University of Pisa, Pisa, Italy
    • ,
  • Godefridus J. Peters

      Affiliations

    • VU University Medical Center, Amsterdam, The Netherlands

Accepted 31 March 2011. published online 06 May 2011.

Highlights

► MiRNAs influence nearly all aspects of health and diseases, including cancer. ► Cancer cells have miRNAs aberrations (deregulated gene expression and mutations). ► MiRNA aberrations affect apoptosis, drug targets, transport or metabolism. ► MiRNAs also regulate cancer stem cells, which are chemoresistant. ► MiRNA profiling can be used to predict drug resistance and customize therapies.

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.

Keywords: microRNA, Chemoresistance, Apoptosis pathways, Drug metabolism, Pharmacogenetics, Cancer stem cells, Clinical outcome

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PII: S1040-8428(11)00089-8

doi:10.1016/j.critrevonc.2011.03.010

Critical Reviews in Oncology / Hematology
Volume 81, Issue 2 , Pages 103-122, February 2012

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