Cancer

Patient sample, cell culture and mouse studies suggest inhibiting MCL1 could help treat triple-negative breast cancer (TNBC) and HER2-amplified breast cancer. In breast cancer patient samples, levels of MCL1 were higher in TNBC and HER2-amplified tumors than in estrogen receptor 1 (ESR1)-positive tumors. In two human TNBC cell lines and a human HER2-amplified breast cancer cell line, a MCL1 inhibitor tool compound decreased viability compared with no treatment. Also in the HER2-amplified human breast cancer cell line, the MCL1 inhibitor plus Herceptin trastuzumab, Tykerb lapatinib or the generic docetaxel decreased viability compared with any agent alone. In two patient-derived xenograft (PDX) mouse models of TNBC, the MCL1 inhibitor plus docetaxel decreased tumor growth and increased survival. In a PDX mouse model of HER2-amplified breast cancer, the MCL1 inhibitor plus Herceptin decreased tumor growth and increased survival. Next steps include testing the combination therapies in breast cancer patients.

Roche, its Genentech Inc. unit and Chugai Pharmaceutical Co. Ltd. market Herceptin, a humanized mAb against HER2, to treat breast and gastric cancers...