BioCentury
ARTICLE | Distillery Therapeutics

Cancer

February 2, 2017 1:46 AM UTC

Mouse studies suggest combining anti-PD-L1 therapies and promoters of reactive oxygen species (ROS) production or agonists of the mTOR or AMPK signaling pathways could help treat colorectal and skin cancers. In a mouse model of colon cancer, an anti-PD-L1 mAb plus either the ROS precursor tert-butyl hydroperoxide or two tool compounds that promote ROS production decreased tumor growth and increased survival compared with the anti-PD-L1 mAb alone. Also in the model, the anti-PD-L1 mAb plus an mTOR or AMPK agonist tool compound decreased tumor growth. In addition, the mAb plus the mTOR pathway agonist oltipraz or the AMPK pathway agonist bezafibrate decreased tumor growth and increased survival in the model. In an orthotopic mouse model of skin cancer, the anti-PD-L1 mAb plus tert-butyl hydroperoxide, oltipraz or one of the tool compounds promoting ROS production increased survival and decreased tumor volume. Next steps include identifying and testing additional ROS promoters and mTOR and AMPK pathway agonists in combination with anti-PD-L1 mAbs in models of colon and skin cancer.

The generic bezafibrate is marketed to treat hyperlipidemia...