Therapeutics: Multiple kinase targets; an undisclosed target

Mouse studies suggest the mitochondrial inhibitor ME-344 and/or the multikinase inhibitor Vargatef nintedanib could help treat kinase inhibitor-resistant cancers. In a mouse model of Stivarga regorafenib-resistant metastatic breast cancer and a patient-derived xenograft mouse model of Stivarga-resistant lung cancer, ME-344 in combination with Stivarga or Vargatef decreased tumor growth compared with any of the agents alone. In a mouse model of Stivarga-resistant lung carcinoma, ME-344 plus Stivarga increased survival. In a mouse model of Vargatef- and phenformin-resistant breast cancer, phenformin combined with Vargatef or the multikinase inhibitor dovitinib lactate decreased tumor growth. Next steps include testing multikinase inhibitors and mitochondrial inhibitors in animal models of other drug-resistant cancers.

MEI Pharma Inc. has ME-344, an isoflavone-derived mitochondrial inhibitor, in Phase I/II testing to treat ovarian and small cell lung cancers and preclinical testing to treat breast cancer. ...