COSMIC collection


Ever since resistance to apoptosis emerged as an influential pathway in cancer, targeting the mechanisms that allow tumours to avoid the same fate as normal cells has been proposed as a potent anticancer strategy. In Cancer Cell, John Reed and colleagues validate this principle by describing how small-molecule inhibitors that remove an important ‘brake’ in apoptosis can strip tumours of their immortality. The ultimate effectors of programmed cell death are the caspase family of proteases. Normally, caspases are kept in check by members of the inhibitor of apoptosis (IAP) family, which bind to and inactivate caspases until they are needed. Caspases are overexpressed in tumours, but so are IAPs, and, therefore, failure to activate caspases could create resistance to apoptosis. So, Reed and colleagues screened a library of around one million compounds for binding to one of the best characterized of the IAPs: XIAP. XIAP inhibits apoptosis at a distal step in the apoptosis pathway — at the convergence of cell-death pathways that are activated by mitochondria-dependent and mitochondriaindependent stimuli. Eight polyphenylurea-based compounds were identified that bind to the BIR2 domain of XIAP

DOI: 10.1038/nrc1314

Cite this paper

@article{Flintoft2004COSMICC, title={COSMIC collection}, author={Louisa Flintoft}, journal={Nature Reviews Cancer}, year={2004}, volume={4}, pages={170-170} }