LSD1 inhibition: a therapeutic strategy in cancer?

Expert Opin Ther Targets. 2012 Dec;16(12):1239-49. doi: 10.1517/14728222.2012.722206. Epub 2012 Sep 8.


Introduction: The role of epigenetic dysfunction in cancer is increasingly appreciated. This has raised the question as to whether enzymes that regulate the structure and function of chromatin might represent novel therapeutic targets. The histone demethylase LSD1 is one such candidate and novel, potent inhibitors are under development.

Areas covered: The literature on LSD1 (also known as KDM1A, AOF2, BHC110 or KIAA0601) was identified in Pubmed and is herein discussed. Areas covered include the structure and enzymatic activity of LSD1, its role in chromatin regulatory complexes, its functional roles in normal and malignant tissue, pharmacological inhibitors of its activity and their putative therapeutic roles.

Expert opinion: Pre-clinical data supporting a therapeutic role for LSD1 inhibitors are most encouraging in acute myeloid leukaemia, although optimal dosing strategies and beneficial combinations with other agents remain unclear. Studies making use of potent, selective LSD1 inhibitors active in the nanomolar range are required to establish therapeutic indications in other subtypes of haematological malignancy, and in solid tumours.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Histone Demethylases / antagonists & inhibitors
  • Histone Demethylases / chemistry
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Humans
  • Neoplasms / metabolism*
  • Protein Conformation


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histone Demethylases
  • KDM1A protein, human