Next-gen approach could help fight pancreatic cancer by altering tumor metabolism

While pancreatic cancer is relatively rare in the U.S., a diagnosis can often mean a death sentence, with the National Cancer Institute pegging the 5-year survival rate at just over 7%. But researchers at the University of Texas Southwestern Medical Center may have found new possibilities for the treatment of pancreatic cancer, starting with CDK4/6 inhibitors.

This class of drugs works by inhibiting the enzymes CDK4 and 6, which promote the growth of cancer cells. Pfizer's Ibrance (palbociclib) won a speedy FDA approval for breast cancer last February, the first of a crowded field of CDK inhibitors to get the regulatory go-ahead.

In a study published in Cell Reports, the UT Southwestern team treated pancreatic tumors and cancer cells grown in mice with CDK4/6 inhibitors and found that the drugs didn't just stop pancreatic cancer cells from proliferating. They also altered the metabolism of the cells, making it more active.

The disrupted cancer cells' metabolism presents a target that researchers can attack with another drug that could exploit the new vulnerability, such as mTOR inhibitors, which target enzymes that regulate metabolism, growth and proliferation. Drugs like Ibrance could become part of a one-two punch to deadly pancreatic cancers.

Erik Knudsen, professor of internal medicine at UT Southwestern

"Now we can try attacking specific aspects of CDK4/6-induced metabolic programming," said Erik Knudsen, a professor of internal medicine at UT Southwestern and a member of the medical center's Harold C. Simmons Comprehensive Cancer Center, in a statement. "For example, 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."

Pfizer ($PFE) may have been the first to get its CDK inhibitor approved, and on Phase II data to boot, but Eli Lilly ($LLY) is in hot pursuit. Lilly received an FDA "breakthrough therapy" designation for its abemaciclib in October and is eyeing an accelerated approval for breast cancer. And Novartis ($NVS) is currently recruiting for a Phase II trial of its LEE011 in certain cancers.

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