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dc.contributor.authorLuo, M-J
dc.contributor.authorPalmieri, M
dc.contributor.authorRiffkin, CD
dc.contributor.authorSakthianandeswaren, A
dc.contributor.authorDjajawi, TM
dc.contributor.authorHirokawa, Y
dc.contributor.authorShuttleworth, V
dc.contributor.authorSegal, DH
dc.contributor.authorWhite, CA
dc.contributor.authorNhu, D
dc.contributor.authorLessene, G
dc.contributor.authorLee, M
dc.contributor.authorGibbs, P
dc.contributor.authorHuang, DCS
dc.contributor.authorSieber, OM
dc.contributor.authorGong, J-N
dc.date.accessioned2020-11-17T03:37:49Z
dc.date.available2020-11-17T03:37:49Z
dc.date.issued2020-09-10
dc.identifierpii: 10.1038/s41419-020-02815-0
dc.identifier.citationLuo, M. -J., Palmieri, M., Riffkin, C. D., Sakthianandeswaren, A., Djajawi, T. M., Hirokawa, Y., Shuttleworth, V., Segal, D. H., White, C. A., Nhu, D., Lessene, G., Lee, M., Gibbs, P., Huang, D. C. S., Sieber, O. M. & Gong, J. -N. (2020). Defining the susceptibility of colorectal cancers to BH3-mimetic compounds. CELL DEATH & DISEASE, 11 (9), https://doi.org/10.1038/s41419-020-02815-0.
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/11343/251562
dc.description.abstractNovel 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 BCLxL and MCL1. Importantly, these in vitro findings were confirmed in a xenograft model and, interestingly, in all (5/5) patient derived tumor organoids evaluated. Our results lend strong support to the notion that BCLxL and MCL1 are highly promising targets for further evaluation in efforts to improve the treatment of colorectal cancers.
dc.languageEnglish
dc.publisherSPRINGERNATURE
dc.titleDefining the susceptibility of colorectal cancers to BH3-mimetic compounds
dc.typeJournal Article
dc.identifier.doi10.1038/s41419-020-02815-0
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.departmentSurgery (RMH)
melbourne.source.titleCell Death and Disease
melbourne.source.volume11
melbourne.source.issue9
dc.rights.licenseCC BY
melbourne.elementsid1464472
melbourne.contributor.authorPalmieri, Michelle
melbourne.contributor.authorSieber, Oliver
melbourne.contributor.authorLessene, Guillaume
melbourne.contributor.authorGibbs, Peter
melbourne.contributor.authorHuang, David
melbourne.contributor.authorWhite, Christine
melbourne.contributor.authorSakthianandeswaren, Anuratha
melbourne.contributor.authorSegal, David
melbourne.contributor.authorLuo, Mingjie
melbourne.contributor.authorRiffkin, Chris
melbourne.contributor.authorDjajawi, Tirta
melbourne.contributor.authorNhu, Duong
melbourne.contributor.authorLee, Margaret
melbourne.contributor.authorGong, Jianan
dc.identifier.eissn2041-4889
melbourne.accessrightsOpen Access


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