Journal article
Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy
JD Leverson, DC Phillips, MJ Mitten, ER Boghaert, D Diaz, SK Tahir, LD Belmont, P Nimmer, Y Xiao, XM Ma, KN Lowes, P Kovar, J Chen, S Jin, M Smith, J Xue, H Zhang, A Oleksijew, TJ Magoc, KS Vaidya Show all
Science Translational Medicine | Published : 2015
Abstract
The BCL-2/BCL-XL/BCL-W inhibitor ABT-263 (navitoclax) has shown promising clinical activity in lymphoid malignancies such as chronic lymphocytic leukemia. However, its efficacy in these settings is limited by thrombocytopenia caused by BCL-XL inhibition. This prompted the generation of the BCL-2-selective inhibitor venetoclax (ABT-199/GDC-0199), which demonstrates robust activity in these cancers but spares platelets. Navitoclax has also been shown to enhance the efficacy of docetaxel in preclinical models of solid tumors, but clinical use of this combination has been limited by neutropenia. We used venetoclax and the BCL-XL-selective inhibitors A-1155463 and A-1331852 to assess the relative..
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Awarded by Independent Research Institutes Infrastructure Support Scheme
Funding Acknowledgements
Work in the Huang Lab is supported by grants and fellowships from the Australian National Health and Medical Research Council (research fellowships to D.C.S.H.; project grants to D.C.S.H.; program grants 461219, 461221, and 1016701; and Independent Research Institutes Infrastructure Support Scheme grant 361646), the Cancer Council Victoria (grant-in-aid to D.C.S.H.), the Leukemia and Lymphoma Society (Specialized Centers of Research grants), the Australian Cancer Research Foundation, and a Victorian State Government Operational Infrastructure Support grant.