Research On Pancreatic Cancer Described By S.N. Hochwald And Colleagues

NewsRx.com

October 1, 2009

"Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that is overexpressed in many types of tumors, including pancreatic cancer, and plays an important role in cell adhesion and survival signaling. Pancreatic cancer is a lethal disease and is very resistant to chemotherapy, and FAK has been shown recently to assist in tumor cell survival," researchers in the United States report.

"Therefore, FAK is an excellent potential target for anti-cancer therapy. We identified a novel small molecule inhibitor (1,2,4,5-Benzenetetraamine tetrahydrochloride, that we called Y15) targeting the main autophosphorylation site of FAK and hypothesized that it would be an effective treatment strategy against human pancreatic cancer. Y15 specifically blocked phosphorylation of Y397-FAK and total phosphorylation of FAK. It directly inhibited FAK autophosphorylation in a dose- and time-dependent manner. Furthermore, Y15 increased pancreatic cancer cell detachment and inhibited cell adhesion in a dose-dependent manner. Y15 effectively caused human pancreatic tumor regression in vivo, when administered alone and its effects were synergistic with gemcitabine chemotherapy. This was accompanied by a decrease in Y397-phosphorylation of FAK in the tumors treated with Y15," wrote S.N. Hochwald and colleagues.

The researchers concluded: "Thus, targeting the Y397 site of FAK in pancreatic cancer with the small molecule inhibitor, 1,2,4,5-Benzenetetraamine tetrahydrochloride, is a potentially effective treatment strategy in this deadly disease."

Hochwald and colleagues published their study in Cell Cycle (A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer. Cell Cycle, 2009;8(15):2435-2443).

For additional information, contact W.G. Cance, Roswell Pk Cancer Institute, Dept. of Surgery, Buffalo, NY 14263, USA.

Publisher contact information for the journal Cell Cycle is: Landes Bioscience, 1002 West Avenue, 2ND Floor, Austin, TX 78701, USA.

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