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Selective Impact Of Cdk4/6 Suppression On Patient-Derived Models Of Pancreatic Cancer., Agnieszka K Witkiewicz, Nicholas A Borja, Jorge Franco, Jonathan Brody, Md, Charles Yeo, John Mansour, Michael A Choti, Peter Mccue, Erik S Knudsen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in …