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dc.contributor.authorLalaoui, N
dc.contributor.authorMerino, D
dc.contributor.authorGiner, G
dc.contributor.authorVaillant, F
dc.contributor.authorChau, D
dc.contributor.authorLiu, L
dc.contributor.authorKratina, T
dc.contributor.authorPal, B
dc.contributor.authorWhittle, JR
dc.contributor.authorEtemadi, N
dc.contributor.authorBerthelet, J
dc.contributor.authorGrasel, J
dc.contributor.authorHall, C
dc.contributor.authorRitchie, ME
dc.contributor.authorErnst, M
dc.contributor.authorSmyth, GK
dc.contributor.authorVaux, DL
dc.contributor.authorVisvader, JE
dc.contributor.authorLindeman, GJ
dc.contributor.authorSilke, J
dc.date.accessioned2020-11-17T03:19:31Z
dc.date.available2020-11-17T03:19:31Z
dc.date.issued2020-04-27
dc.identifierpii: 10.1038/s41418-020-0541-0
dc.identifier.citationLalaoui, N., Merino, D., Giner, G., Vaillant, F., Chau, D., Liu, L., Kratina, T., Pal, B., Whittle, J. R., Etemadi, N., Berthelet, J., Grasel, J., Hall, C., Ritchie, M. E., Ernst, M., Smyth, G. K., Vaux, D. L., Visvader, J. E., Lindeman, G. J. & Silke, J. (2020). Targeting triple-negative breast cancers with the Smac-mimetic birinapant. Cell Death and Differentiation, 27 (10), pp.2768-2780. https://doi.org/10.1038/s41418-020-0541-0.
dc.identifier.issn1350-9047
dc.identifier.urihttp://hdl.handle.net/11343/251470
dc.description.abstractSmac mimetics target inhibitor of apoptosis (IAP) proteins, thereby suppressing their function to facilitate tumor cell death. Here we have evaluated the efficacy of the preclinical Smac-mimetic compound A and the clinical lead birinapant on breast cancer cells. Both exhibited potent in vitro activity in triple-negative breast cancer (TNBC) cells, including those from patient-derived xenograft (PDX) models. Birinapant was further studied using in vivo PDX models of TNBC and estrogen receptor-positive (ER+) breast cancer. Birinapant exhibited single agent activity in all TNBC PDX models and augmented response to docetaxel, the latter through induction of TNF. Transcriptomic analysis of TCGA datasets revealed that genes encoding mediators of Smac-mimetic-induced cell death were expressed at higher levels in TNBC compared with ER+ breast cancer, resulting in a molecular signature associated with responsiveness to Smac mimetics. In addition, the cell death complex was preferentially formed in TNBCs versus ER+ cells in response to Smac mimetics. Taken together, our findings provide a rationale for prospectively selecting patients whose breast tumors contain a competent death receptor signaling pathway for the further evaluation of birinapant in the clinic.
dc.languageEnglish
dc.publisherSpringer Nature
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTargeting triple-negative breast cancers with the Smac-mimetic birinapant
dc.typeJournal Article
dc.identifier.doi10.1038/s41418-020-0541-0
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.departmentSchool of Mathematics and Statistics
melbourne.affiliation.departmentMedicine (RMH)
melbourne.affiliation.departmentSurgery (RMH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.affiliation.facultyScience
melbourne.source.titleCell Death and Differentiation
melbourne.source.volume27
melbourne.source.issue10
melbourne.source.pages2768-2780
dc.rights.licenseCC BY
melbourne.elementsid1447609
melbourne.contributor.authorLindeman, Geoffrey
melbourne.contributor.authorErnst, Matthias
melbourne.contributor.authorRitchie, Matthew
melbourne.contributor.authorVaux, David
melbourne.contributor.authorSmyth, Gordon
melbourne.contributor.authorSilke, John
melbourne.contributor.authorPal, Bhupinder
melbourne.contributor.authorMerino, Delphine
melbourne.contributor.authorLalaoui, Najoua
melbourne.contributor.authorEtemadi, Nima
melbourne.contributor.authorVaillant, Francois
melbourne.contributor.authorVisvader, Jane
melbourne.contributor.authorGiner, Goknur
melbourne.contributor.authorLiu, Lin
melbourne.contributor.authorWhittle, James Richard
dc.identifier.eissn1476-5403
melbourne.accessrightsOpen Access


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