Therapeutics:Cyclin dependent kinase 4 (CDK4); CDK6; mammalian target of rapamycin (mTOR; FRAP; RAFT1)

Cell culture and mouse studies suggest combining dual CDK4/CDK6 inhibitors with inhibitors of MEK or mTOR could help treat pancreatic ductal adenocarcinoma (PDAC). In a human PDAC cell line, Ibrance palbociclib plus the MEK inhibitor selumetinib increased cell cycle arrest and decreased cell growth compared with selumetinib alone. In a xenograft mouse model of PDAC, Ibrance plus the mTOR inhibitor BEZ235 decreased tumor growth compared with either agent alone. Next steps could include testing CDK4/CDK6 inhibitors in combination with MEK or mTOR inhibitors in other cancer models.

Pfizer Inc. and Amgen Inc. market Ibrance, an oral small molecule inhibitor of CDK4 and CDK6, to treat breast cancer. Pfizer and Amgen also have Ibrance in Phase II testing to treat sarcoma and brain cancer and in preclinical testing to treat melanoma...