A two-drug combo that matches Afinitor with an experimental compound proved effective in killing pancreatic cancer cells and blunting tumor growth in cell lines and mouse models for the lethal disease.
Investigators at the University of Florida combined Afinitor with a synthetic compound coded PF-04554787. They targeted a protein known as focal adhesion kinase, or FAK, which triggers an enzyme called AKT, which in turn assist in the survival of islet cells in the pancreas. When islet cells start turning into tumors, the FAK protein is overproduced, helping pancreatic neuroendocrine tumors to resist chemo.
Only a small percent of patients with pancreatic neuroendocrine tumors respond to Afinitor, inspiring their search for a combo that would work among far more patients.
"Once we figured out that FAK was important, we started looking for drug combinations that would increase efficacy," said Rony François, an M.D./Ph.D. student working with Maria Zajac-Kaye, an associate professor in the UF College of Medicine's department of anatomy and cell biology.
By itself, the drug reduced tumor volume in mice by 50%, and worked far better than Afinitor alone when it was combined with the approved drug. The results were published in the Journal of the National Cancer Institute.
"This is important because we're focused on everolimus, a drug that is already approved, non-toxic and given to patients. Anything that we can do to make it better represents a big improvement," François said.
There are no immediate plans to test the combo in humans, the investigators note. But they would like to try it.
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