Cancer cells in mantle cell lymphoma (MCL) undergo uncontrolled proliferation due to overproduction of the protein Cyclin D1. The family of proteins called Cyclins combine with enzymes called Cyclin dependent kinases (Cdk) in a way that is analgous to gas in an engine. The Cdks are the engine but they rely on the Cyclins to make them work.
PD0332991 is an orally bioavailable (i.e., a pill) inhibitor of Cdk4/6, the Cdks that combine with Cyclin D1 in MCL. A recently published clinical trial performed at Weill Cornell Medical College and other sites around the United States demonstrated that PD0332991 could successfully stop MCL tumors from growing in several patients, including one response that lasted for more than 30 months. Biopsies taken from patients while receiving PD0332991 revealed that Cdk4/6 was effectively inhibited while a specialized kind of imaging, called FLT-PET, demonstrated that MCL cells had stopped proliferating. Although these results were promising, not every patient benefited, and the responses were not permanent.
Additional studies combining PD0332991 with other drugs based on promising laboratory data are currently underway at Weill Cornell. Click here for more information.