Research ArticleCancer

Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer

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Science Translational Medicine  02 Aug 2017:
Vol. 9, Issue 401, eaam7049
DOI: 10.1126/scitranslmed.aam7049

Cutting off another tumor lifeline

BH3 mimetics are drugs that inhibit the BCL-2 family of prosurvival proteins in cancer cells and thereby promote cancer cell death. Unfortunately, MCL-1, a member of this prosurvival family, can interfere with treatment because it is not sensitive to currently available BH3 mimetics. The MCL-1 inhibitor S63845 was developed to overcome this mechanism of treatment resistance, and Merino et al. examined the effectiveness of this drug in cell lines and xenografts derived from breast cancer patients. The authors demonstrated the drug’s efficacy in combination with several drugs that are already in clinical use and also identified a protein that can promote treatment resistance, which may help predict which patients are more likely to benefit from the new treatment.

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