Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function

J Clin Invest. 2005 Oct;115(10):2673-8. doi: 10.1172/JCI26251.

Abstract

Recent studies have shown that members of the inhibitor of apoptosis (IAP) protein family are highly expressed in several classes of cancer. The primary implication of these findings is that the elevated expression of IAPs is not coincidental but actually participates in oncogenesis by helping to allow the malignant cell to avoid apoptotic cell death. This concept, together with the discovery of several IAP-regulatory proteins that use a conserved mode of action, has stimulated a major effort by many research groups to devise IAP-targeting strategies as a means of developing novel antineoplastic drugs. In this Review, we consider the evidence both for and against the IAPs being valid therapeutic targets, and we describe the types of strategies being used to neutralize their functions.

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.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Apoptosis*
  • Drug Delivery Systems / methods
  • Drug Design
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Neoplasm Proteins / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*

Substances

  • Antineoplastic Agents
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins