Targeting apoptosis pathways for new cancer therapeutics

Annu Rev Med. 2014:65:139-55. doi: 10.1146/annurev-med-010713-141310. Epub 2013 Nov 4.


The past decade has witnessed tremendous advances in the discovery and development of novel small-molecule inhibitors targeting apoptosis pathways for cancer treatment, with some compounds now in clinical development. Early promising clinical data have been reported with these new classes of anticancer drugs. This review highlights the recent advancements in the development of small-molecule inhibitors targeting three major classes of antiapoptotic proteins: antiapoptotic B cell lymphoma 2 (BCL-2) proteins, inhibitor of apoptosis proteins (IAPs), and murine double-minute 2 (MDM2). Special emphasis is given to those that have been advanced into clinical trials. The challenges and future directions in the further preclinical and clinical development of these new anticancer drugs are also discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
  • Signal Transduction


  • Antineoplastic Agents
  • Inhibitor of Apoptosis Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2