Journal article

Defining the susceptibility of colorectal cancers to BH3-mimetic compounds

Ming-Jie Luo, Michelle Palmieri, Chris D Riffkin, Anuratha Sakthianandeswaren, Tirta Mario Djajawi, Yumiko Hirokawa, Victoria Shuttleworth, David H Segal, Christine A White, Duong Nhu, Guillaume Lessene, Margaret Lee, Peter Gibbs, David CS Huang, Oliver M Sieber, Jia-nan Gong



Novel targets are required to improve the outcomes for patients with colorectal cancers. In this regard, the selective inhibitor of the pro-survival protein BCL2, venetoclax, has proven highly effective in several hematological malignancies. In addition to BCL2, potent and highly selective small molecule inhibitors of its relatives, BCLxL and MCL1, are now available, prompting us to investigate the susceptibility of colorectal cancers to the inhibition of one or more of these pro-survival proteins. While targeting BCLxL, but not BCL2 or MCL1, on its own had some impact, most (15/17) of the immortalized colorectal cancer cell lines studied were efficiently killed by the combined targeting of ..

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Awarded by Australian National Health and Medical Research Council (NHMRC)

Funding Acknowledgements

We thank Z. Xu, R. Thijssen, M.F. van Delft, and S. Huang for helpful discussions and suggestions. This work is supported by scholarships, fellowships, and grants from the Australian National Health and Medical Research Council (NHMRC) (Research Fellowships 1136119 to O.M.S. and 1156024 to D.C.S.H.; Program Grant 1113133 to D.C.S.H.), Melbourne University (MIRS and MIFRS scholarships to T.M.D.), the China Scholarship Council (M.-J.L.), the Stafford Fox Medical Research Foundation (O.M.S.), and the Australian Cancer Research Foundation. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS).