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Drug Inhibits Pancreatic Tumor Growth

Inhibitor of Src shows promise in human pancreatic tumor cell lines

September 3, 2010 | Melissa Marino

With a 5-year survival of less than 5 percent, pancreatic cancer is one of the most lethal forms of cancer, and conventional chemotherapy offers only a modest survival benefit. Drugs that inhibit the proto-oncogene Src have shown promise in animal models of pancreatic cancer, but their molecular actions are not well understood.

In the August issue of Molecular Cancer Therapeutics, Nipun Merchant, M.D., Nagaraj Nagathihalli, Ph.D., and colleagues report the molecular effects of the Src inhibitor dasatinib – a drug approved to treat some leukemias – in human pancreatic cancer cell lines.

They found that dasatinib stimulates cell death (apoptosis) and inhibits cell proliferation, migration and invasion through multiple signaling pathways in cultured cells, which correlated to reduced tumor growth in mice with implanted pancreatic tumors. The study also demonstrated for the first time that Src localization within the cell impacts patient survival, with increased membrane expression associated with decreased survival.

The findings establish a rationale for Src inhibition in treating pancreatic cancer and identify possible biomarkers for resistance to dasatinib treatment.

For other research highlights from Vanderbilt University Medical Center laboratories, see ‘Aliquots‘ in the VUMC Reporter.