Guest Open Access Plus | Free Content | About | Sign in | New Users: Sign up | Mark List  

Current Molecular Medicine

Volume 8 Issue 2
ISSN: 1566-5240
eISSN: 1875-5666

 

   All Titles

  Unique Biology of Mcl-1: Therapeutic Opportunities in Cancer
  pp.138-147 (10) Authors: Gordon C. Shore, Matthew R. Warr
 
 
      Abstract

Accumulating evidence suggests that Mcl-1 plays a critical pro-survival role in the development and maintenance of both normal and malignant tissues. Regulation of Mcl-1 expression occurs at multiple levels, allowing for either the rapid induction or elimination of the protein in response to different cellular events. This suggests that Mcl-1 can play an early role in response to signals directing either cell survival or cell death. Deregulation of pathways regulating Mcl-1 that result in its over-expression likely contribute to a cell's inability to properly respond to death signals possibly leading to cell immortalization and tumorigenic conversion. Correspondingly, Mcl-1 has been shown to be up-regulated in numerous hematological and solid tumor malignancies. Moreover, this up-regulation appears to be a factor in the resistance of some cancer types to conventional cancer therapies. Mechanisms that abrogate the pro-survival function of Mcl-1 either by diminishing its levels or inactivating its functional BH3 groove have shown promise for the combinational treatment with existing cancer therapies and as single agents in certain malignancies. Here we review the various pathways that regulate Mcl-1 expression and describe agents that are currently under development to modulate Mcl-1 activity for therapeutic benefit in oncology.

 
  Keywords: Cancer, apoptosis, Bcl-2 family, Mcl-1, Mcl-1 targeted therapeutics
  Affiliation: Department of Biochemistry,McIntyre Medical Sciences Building, McGill University,3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6,Canada.
 
  Key: New Content Free Content Open Access Plus Subscribed Content

Bentham Science Publishers
www.benthamscience.com

 

  Copyright © 1994 - 2014   Bentham Science Publishers