BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: MEK; BRAF

October 13, 2016 7:00 AM UTC

Patient sample, cell culture and mouse studies suggest combining digitoxin or digoxin with MEK and/or BRAF inhibitors could help treat melanoma and AML. In primary tumor cells from three melanoma patients, digitoxin or digoxin decreased cell numbers compared with vehicle. In patient-derived xenograft mouse models of melanoma, the MEK inhibitor Mekinist trametinib plus digitoxin or digoxin decreased tumor growth and increased survival compared with any agent alone. Also in the model, digitoxin plus the BRAF inhibitor Zelboraf vemurafenib decreased tumor growth compared with vehicle. In patient-derived xenograft mouse models of BRAF-mutant melanomas, the combination of the BRAF inhibitor Tafinlar, Mekinist and digoxin decreased tumor growth compared with Tafinlar plus Mekinist, Tafinlar plus digoxin, or Tafinlar alone. In a xenograft mouse model of AML, digitoxin plus Mekinist decreased tumor growth and increased survival compared with either agent alone. Next steps could include testing digitoxin and digoxin in models of other cancers.

Japan Tobacco Inc. and Novartis AG market Mekinist for melanoma and have the compound in Phase I through Phase II testing for various other cancers...