'Did He Who Made the Lamb Make Thee?' New Developments in Treating the 'Fearful Symmetry' of Acute Myeloid Leukemia

Trends Mol Med. 2017 Mar;23(3):264-281. doi: 10.1016/j.molmed.2017.01.005. Epub 2017 Feb 11.

Abstract

Malignant cells must circumvent endogenous cell death pathways to survive and develop into cancers. Acquired cell death resistance also sets up malignant cells to survive anticancer therapies. Acute Myeloid Leukemia (AML) is an aggressive blood cancer characterized by high relapse rate and resistance to cytotoxic therapies. Recent collaborative profiling projects have led to a greater understanding of the 'fearful symmetry' of the genomic landscape of AML, and point to the development of novel potential therapies that can overcome factors linked to chemoresistance. We review here the most recent research in the genetics of AML and how these discoveries have led, or might lead, to therapies that specifically activate cell death pathways to substantially challenge this 'fearful' disease.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Death / drug effects*
  • DNA Modification Methylases / antagonists & inhibitors
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Molecular Targeted Therapy / methods
  • Peptidomimetics / pharmacology
  • Peptidomimetics / therapeutic use
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • Peptidomimetics
  • Protein Kinase Inhibitors
  • DNA Modification Methylases