The relationship between platinum drug resistance and epithelial-mesenchymal transition

Arch Toxicol. 2017 Feb;91(2):605-619. doi: 10.1007/s00204-016-1912-7. Epub 2016 Dec 28.

Abstract

One of the most commonly used chemotherapeutics, platinum drugs are used to treat a wide range of cancer types. Although many cancers initially respond well to those drugs, drug resistance occurs frequently and different molecular mechanisms have been associated with it. However, predictive biomarkers of cellular response in specific tumour types still do not exist. Epithelial-mesenchymal transition (EMT) is a malignant cancer phenotype characterized by aggressive invasion and metastasis, and resistance to apoptosis. Recent studies indicate that EMT accompanies the development of drug resistance to a number of cancer chemotherapies. The link between these two phenomena is still not elucidated, although several important molecules involved in both these complex processes, such as transcription factors (SNAIL, TWIST, ZEB, etc.) and miRNAs (miRNA-200 family, miR-15, miR-186, etc.) have been recognized as important. This article reviews numerous unresolved issues regarding platinum drugs resistance and EMT, the complexity of the signalling networks that regulate those two phenomena and their importance in tumour response and spreading which are becoming focuses of interest of many scientists. This article also presents molecules involved in platinum resistance and EMT as possible targets for new cancer therapy.

Keywords: Cisplatin; Drug resistance; Epithelial–mesenchymal transition; Platinum drugs; Tumour.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / physiology*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Antineoplastic Agents
  • MicroRNAs
  • Transcription Factors
  • Cisplatin