Annexin A4 is a promising therapeutic target for the treatment of platinum-resistant cancers

Expert Opin Ther Targets. 2014 Apr;18(4):403-14. doi: 10.1517/14728222.2014.882323. Epub 2014 Jan 30.

Abstract

Introduction: Platinum drugs are widely used for the treatment of testicular, bladder, ovarian, colorectal, lung and prostate cancers. With regard to ovarian cancer in particular, the prognosis is poor for tumours that are (or have become) platinum-resistant. Determining the mechanism underlying platinum resistance may aid in the identification of therapeutic targets for the treatment of platinum-resistant tumours.

Areas covered: This review gives an overview of the characteristics and functions of Annexin (Anx) A4, the mechanism of Anx A4-induced platinum resistance, the association between platinum resistance and platinum transporters, recent reports that Anx A4 overexpression promotes the efflux of platinum drugs via platinum transporters and the association between other Anxs and chemoresistance. The reader will gain an understanding of recent studies on the mechanism of Anx A4-induced chemoresistance. Anx A4 represents a therapeutic target for the treatment of Anx A4-overexpressing platinum-resistant tumours.

Expert opinion: Anx A4 is overexpressed in ovarian clear cell carcinoma (CCC), and enhanced Anx A4 expression induces platinum resistance. Recent studies showed that Anx A4 is also associated with platinum resistance in cancers other than ovarian CCC. Furthermore, other Anxs are reportedly associated with chemoresistance, suggesting a relationship between the Anx family and chemoresistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Annexin A4 / antagonists & inhibitors
  • Annexin A4 / metabolism*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Drug Delivery Systems / methods*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Platinum Compounds / administration & dosage
  • Platinum Compounds / metabolism*
  • Protein Binding / physiology
  • Treatment Outcome

Substances

  • Annexin A4
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Platinum Compounds