Journal article

The combination of reduced MCL-1 and standard chemotherapeutics is tolerable in mice

Kerstin Brinkmann, Stephanie Grabow, Craig D Hyland, Charis E Teh, Warren S Alexander, Marco J Herold, Andreas Strasser



A common therapeutic strategy to combat human cancer is the use of combinations of drugs, each targeting different cellular processes or vulnerabilities. Recent studies suggest that addition of an MCL-1 inhibitor to such anticancer drug treatments could be an attractive therapeutic strategy. Thus, it is of great interest to understand whether combinations of conventional anticancer drugs with an MCL-1 inhibitor will be tolerable and efficacious. In order to mimic the combination of MCL-1 inhibition with other cancer therapeutics, we treated Mcl-1+/- heterozygous mice, which have a ~50% reduction in MCL-1 protein in their cells, with a broad range of chemotherapeutic drugs. Careful monitoring..

View full abstract


Awarded by NHMRC

Awarded by NHMRC Independent Research Institutes Infrastructure Support Scheme Grant

Awarded by LLS SCOR grant

Awarded by CCV grant

Funding Acknowledgements

We thank K Hughes, C D'Alessandro, K McKenzie, T Krtson, C Gatt and G Siciliano for expert animal care; B Helbert and K Mackwell for genotyping; J Corbin and J McManus for automated blood analysis; E Tsui, V Orlando, K Weston, Y Hoang, C Tsui, S Ter for help with histology, S Monard and his team for help with flow cytometry and P Bouillet for providing Mcl-1<SUP>+/-</SUP> mice and helping with histology assessment, D Grey for his advice for the intracellular FACS analysis of BCL-2 family members and for providing the relevant antibodies and staining solutions. This work was supported by grants and fellowships from the Deutsche Krebshilfe (Dr. Milded-Scheel-post-doctoral fellowship to KB) NHMRC feliowship (1020363), NHMRC program grant (1016701), LLS SCOR grant (7001-13) and CCV grant (1052309) (all to AS). Cancer Council Victoria Venture Grant and Victorian Cancer Agency (VCATRP13041) (to MJH) NHMRC Feliowship (1058344), NHMRC Program Grant (1113577), NHMRC Independent Research Institutes Infrastructure Support Scheme Grant (361646), the Australian Cancer Research Fund and Victorian State Government Operational Infrastructure Support (all to WSA),