Journal article
The BCL-2 protein family, BH3-mimetics and cancer therapy
ARD Delbridge, A Strasser
Cell Death and Differentiation | Published : 2015
DOI: 10.1038/cdd.2015.50
Abstract
Escape from apoptosis is a key attribute of tumour cells and facilitates chemo-resistance. The 'BCL-2-regulated' or 'intrinsic' apoptotic pathway integrates stress and survival signalling to govern whether a cancer cell will live or die. Indeed, many pro-apoptotic members of the BCL-2 family have demonstrated tumour-suppression activity in mouse models of cancer and are lost or repressed in certain human cancers. Conversely, overexpression of pro-survival BCL-2 family members promotes tumorigenesis in humans and in mouse models. Many of the drugs currently used in the clinic mediate their therapeutic effects (at least in part) through the activation of the BCL-2-regulated apoptotic pathway. ..
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Awarded by Leukemia and Lymphoma Society
Funding Acknowledgements
We thank Dr. JM Adams, Dr. S Cory, Dr. P Bouillet, Dr. M Herold, Dr. D Gray, Dr. LA O'Reilly, Dr. S Grabow, Dr. G Kelly, Dr. A Janic, Dr. S Alvarez-Diaz, Dr. F Ke, Dr. B Aubrey, Dr. LValente, Dr. C Vandenberg, Dr. A Kueh, J Low, L Rohrbeck, R Schenk, M Brennan, R Salvamoser and B Yang for insightful discussions. This work was supported by grants and fellowships from the Cancer Council of Victoria (ARDD, Sydney Parker Smith Postdoctoral Research Fellowship), the National Health and Medical Research Council (Program Grant no. 1016701; NHMRC SPRF Fellowship 1020363 to AS) and the Leukemia and Lymphoma Society (SCOR Grant no. 7001-13), Australian Postgraduate Award (to ARDD) and Cancer Therapeutics CRC Top-up Scholarship (to ARDD). This work was made possible by operational infrastructure grants through the Australian Government IRISS and the Victorian State Government OIS.