Subset of Pancreatic Cancer Patients May Benefit from Anti-Angiogenesis Approaches and Targeting of Jak1, Jak2, and Stat3 Pathways to Alter Tumor-Stimulating Effect of Molecules Released from Blood Vessel Endothelial Cells

Cancer researchers at Indiana University report that approximately 15 percent of people with pancreatic cancer may benefit from therapy targeting a newly identified gene signature associated with up-regulated angiogenesis. Using data from The Cancer Genome Atlas (TCGA), Murray Korc, M.D., the Myles Brand Professor of Cancer Research at the Indiana University School of Medicine and a researcher at the Indiana University Melvin and Bren Simon Cancer Center, and colleagues found that a sub-group of pancreatic cancer patients who possess a strong angiogenic gene signature could benefit from personalized therapies that cut off the angiogenic pathways that feed the cancer's growth. This particular gene signature is associated with enabling abnormal blood vessels to form in tumors, which feeds the tumor's growth. The finding, published online on February 25, 2015 in Oncotarget, is new because the prevalence of this signature was not previously known. The authors also demonstrated, for the first time, that endothelial cells, the main type of cell found in the inside lining of blood vessels, can produce molecules that directly stimulate the growth of pancreatic cancer cells. "We showed that endothelial cells can stimulate the growth of pancreatic cancer cells and that by silencing or inhibiting certain pathways--JAK1-2 and STAT3--we can alter that effect," Dr. Korc explained. "We demonstrated that it is possible to target these pathways and prolong the survival of genetically modified mice whose pancreatic cancers also have a strong pro-angiogenic gene signature." Thus, for pancreatic patients with a strong pro-angiogenic gene signature, the finding suggests that they may benefit from targeted therapy that is directed against one of these pathways.
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