Journal
EXPERT REVIEWS IN MOLECULAR MEDICINE
Volume 12, Issue -, Pages -Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S1462399410001572
Keywords
-
Funding
- Canadian Institute of Health Research (CIHR) [FRN12517]
- Canada Research Chair
- Ontario Institute for Cancer Research
Ask authors/readers for more resources
Inhibiting apoptosis is widely accepted as a necessary step in the transition from normal to cancer cells, and most cancer therapies exert their effects by indirectly reversing this process. Commitment to apoptosis is caused by permeabilisation of the outer mitochondrial membrane - a process regulated by the binding between different members of the Bcl-2 family. Furthermore, Bcl-2 family members also bind to the endoplasmic reticulum, where they modify processes such as the unfolded-protein response and autophagy that also cause or modify different types of cell death. With the growing understanding of the importance of the Bcl-2 family as crucial regulators of the decision to initiate apoptosis, much effort has been directed at developing small molecules that modify function by directly binding to Bcl-2 proteins. Preclinical experiments have confirmed that these agents kill cancer cells and overcome chemotherapy resistance. Two of these drugs are in the initial stages of clinical development (ABT-263 and obatoclax), and early results show clinical efficacy at tolerable doses. Important questions for the future include the role of these drugs as monotherapy versus combination therapy with other anticancer drugs, and the related issue of the relative toxicity to cancerous versus normal cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available