Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Department of Medical Biology, Molecular Genetics of Cancer Division, University of Melbourne, Melbourne, VIC, Australia.
Cell Death Differ. 2017 Dec;24(12):2032-2043. doi: 10.1038/cdd.2017.125. Epub 2017 Aug 11.
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.
一种常见的治疗人类癌症的策略是使用药物组合，每种药物针对不同的细胞过程或弱点。最近的研究表明，将 MCL-1 抑制剂添加到这种抗癌药物治疗中可能是一种有吸引力的治疗策略。因此，了解常规抗癌药物与 MCL-1 抑制剂的组合是否可耐受且有效非常重要。为了模拟 MCL-1 抑制与其他癌症治疗方法的联合，我们用广泛的化疗药物治疗 Mcl-1 杂合子小鼠，这些小鼠的细胞中 MCL-1 蛋白减少了约 50%。对治疗小鼠的仔细监测表明，广泛的化疗药物对 Mcl-1 小鼠的整体健康状况没有明显影响，对包括造血组织、心脏、肝脏和肾脏在内的广泛组织没有明显的损伤。这些结果表明，即使与某些细胞毒性药物联合使用，MCL-1 抑制也可能代表一种可耐受的癌症治疗策略。
