Cancer

Cell culture and mouse studies suggest combining MCL1 inhibitors with inducers of double-strand break stress could help treat NSCLC. In an irradiated human NSCLC cell line, MCL1 knockout decreased repair of radiation-induced double-strand breaks compared with normal MCL1 expression. Also in the cell line, a tool compound MCL1 inhibitor plus Lynparza olaparib -- which induces double-strand breaks -- decreased double-strand break repair and tumor colony survival compared with vehicle. In a xenograft mouse model of NSCLC, the MCL1 inhibitor plus Lynparza decreased tumor cell proliferation and tumor growth compared with either agent alone or vehicle. Next steps could include testing MCL1 inhibitors in combination with other inducers of double-strand breaks in NSCLC models.

Merck & Co. Inc. markets Lynparza, a PARP inhibitor, for ovarian cancer and has it approved for breast cancer and in Phase I through Phase III testing for a variety of solid cancers...