The metabolism of pancreatic cancer cells is altered by the anticancer activity of CDK4/6 inhibitors. Researchers hope this biologic vulnerability could be exploited to treat pancreatic cancer, according to initial findings from cultured cells and mice reported in Cell Reports (doi:10.1016/j.celrep.2015.12.094).

Pancreatic cancer is the third-leading cause of cancer deaths in the United States and nearly 49 000 new cases were expected in the United States in 2015, according to the National Cancer Institute. Prognosis is one of the poorest of any cancer, so researchers have sought better treatment options for years.

The first cyclin-dependent kinase 4/6 (CDK4/6), palbociclib (Ibrance), was approved by the FDA last year for a certain type of advanced breast cancer. Drugs in this class are widely studied in clinical trials for many types of cancer, including breast cancer. Described as cytostatic, CDK4/6 inhibitors prevent cancer cells from growing and dividing.

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This study involved treating human pancreatic cancer cells and tumors grown in mice with CDK4/6-inhibiting drugs. Treating the tumor cells with CDK4/6 inhibitors led to the cells having a more active metabolism.

“Now we can try attacking specific aspects of CDK4/6-induced metabolic programming,” said Erik Knudsen, PhD, professor of Internal Medicine in the Eugene McDermott Center for Human Growth and Development at University Texas Southwestern in Dallas, and senior author of the study.

“By targeting altered tumor metabolism, we could potentially turn the cytostatic effect of CDK4/6 inhibitors into a cytotoxic effect that actually kills the cancer cells.”

Disrupting a tumor’s cell cycle with CDK4/6 inhibitors may allow the altered metabolism to be targeted with other drugs such as mTOR inhibitors. The authors conclude therapeutically targeting select features of cells arrested by CDK4/6 inhibitors is feasible.