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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 FEBS+J 2016 ; 283 (14): 2661-75 Nephropedia Template TP
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Attacking Cancer?s Achilles Heel: Antagonism of Anti-Apoptotic BCL-2 Family Members #MMPMID26293580
Opferman JT
FEBS J 2016[Jul]; 283 (14): 2661-75 PMID26293580show ga
Malignant cells routinely violate cellular checkpoints that should initiate cell death in normal cells by triggering pro-apoptotic members of the BCL-2 family of proteins. To escape such death inducing signals, cancer cells often select for up regulation of anti-apoptotic BCL-2 family members including BCL-2, BCL-XL, BFL-1, BCL-W, and MCL-1. These family members prevent death by sequestering pro-apoptotic molecules. To counter this resistance mechanism, small molecule inhibitors of anti-apoptotic BCL-2 family members have been under development. These molecules have shown promise in pre-clinical and clinical testing to overcome apoptotic resistance, prompting cancer cells to undergo apoptosis. Alternatively, other strategies have taken advantage of the normal regulatory machinery controlling anti-apoptotic molecules and have used inhibitors of signaling pathways to down-modulate the expression of anti-apoptotic molecules thus tilting the balance in cancer cells to cell death. This review explores recent developments and strategies aimed at antagonizing anti-apoptotic BCL-2 family member action to promote the induction of cell death in cancer therapy.