Cancer

Cell culture and mouse studies suggest activating PP2A could help treat KRAS-mutant lung cancer. In two human KRAS-mutant lung cancer lines, a previously reported tricyclic sulfonamide-based PP2A activator plus the MEK inhibitor selumetinib decreased proliferation and increased apoptosis compared with selumetinib alone. In two xenograft mouse models of KRAS-mutant lung cancer, the PP2A activator plus selumetinib decreased tumor cell proliferation and tumor volume and increased tumor cell death. In a xenograft mouse model of KRAS-mutant lung cancer resistant to MEK inhibitors, the PP2A activator decreased tumor volume compared with vehicle. Next steps by Rappta Therapeutics LLC include seeking partners to develop the PP2A activator and other analogs in its series.

Array BioPharma Inc., AstraZeneca plc and Merck & Co. Inc. have selumetinib in Phase III testing to treat neurofibromatosis and in Phase II testing to treat various cancers. ...