Differentiation therapy revisited

Nat Rev Cancer. 2018 Feb;18(2):117-127. doi: 10.1038/nrc.2017.103. Epub 2017 Dec 1.

Abstract

The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic leukaemia (APL), a condition that is now highly curable by the combination of retinoic acid (RA) and arsenic. Recently, drugs that trigger differentiation in a variety of primary tumour cells have been identified, suggesting that they are clinically useful. This Opinion article analyses the basis for the clinical successes of RA or arsenic in APL by assessing the respective roles of terminal maturation and loss of self-renewal. By reviewing other successful examples of drug-induced tumour cell differentiation, novel approaches to transform differentiating drugs into more efficient therapies are proposed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Arsenic Trioxide / therapeutic use
  • Cell Differentiation / drug effects*
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / physiopathology
  • Tretinoin / therapeutic use

Substances

  • Antineoplastic Agents
  • Tretinoin
  • Arsenic Trioxide