The combination of reduced MCL-1 and standard chemotherapeutics is tolerable in mice
- Author(s)
- Brinkmann, K; Grabow, S; Hyland, CD; Teh, CE; Alexander, WS; Herold, MJ; Strasser, A;
- Journal Title
- Cell Death and Differentiation
- Publication Type
- Journal Article in press
- Abstract
- 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 of treated mice revealed that a wide range of chemotherapeutic drugs had no significant effect on the general well-being of Mcl-1+/- mice with no overt damage to a broad range of tissues, including the haematopoietic compartment, heart, liver and kidney. These results indicate that MCL-1 inhibition may represent a tolerable strategy in cancer therapy, even when combined with select cytotoxic drugs.Cell Death and Differentiation advance online publication, 11 August 2017; doi:10.1038/cdd.2017.125.
- Publisher
- Springer Nature
- Research Division(s)
- Molecular Genetics Of Cancer; Cancer And Haematology
- PubMed ID
- 28800129
- Publisher's Version
- https://doi.org/10.1038/cdd.2017.125
- NHMRC Grants
- NHMRC/1020363, NHMRC/1016701, NHMRC/1058344, NHMRC/1113577,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-08-30 02:22:18
Last Modified: 2017-09-04 01:29:57