Blood pressure drugs could help halt pancreatic cancer spread, Jefferson researchers find
(PHILADELPHIA) Common blood pressure medications might help block the spread of pancreatic cancer, researchers at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have found. The scientists showed in laboratory studies that two types of pressure-lowering drugs – ACE inhibitors and AT1R blockers – may help reduce the development of tumor-feeding blood vessels, a process called angiogenesis. Such drugs, they say, may become part of a novel strategy to control the growth and spread of cancer.
According to Hwyda Arafat, M.D., Ph.D., assistant professor of surgery at Jefferson Medical College, previous studies have linked a lower cancer incidence with the inhibition of the pancreas hormone angiotensin II (Ang II) by either ACE (Angiotensin I converting enzyme) inhibitors or AT1R (Ang II type 1 receptor) blockers. Ang II increases the production of VEGF, a vascular factor that promotes blood vessel growth in a number of cancers. High VEGF levels have been correlated with poor cancer prognosis and early recurrence. ACE is the enzyme that converts Ang I to Ang II.
Dr. Arafat and her co-workers examined the protein of both invasive pancreatic cancer and normal pancreatic tissue, analyzing the expression of ACE and AT1R in relation to VEGF. They also looked at the effects of blood pressure drugs captopril, an ACE inhibitor, and losartan, an AT1R blocker, on VEGF production in cancer cell lines.
They found that protein levels in ACE and AT1R were significantly higher in 75 percent of the cancer tissue examined. VEGF expression was higher in cases where there was strong ACE and AT1R levels. In the test tube, Ang II significantly enhanced VEGF production in AT1R-positive cells. Captopril and losartan both blocked this effect.
"Our data show for the first time that both ACE and AT1R are functionally expressed in pancreatic ductal adenocarcinoma and suggest their involvement in tumor angiogenesis," Dr. Arafat says. She presents her results December 5, 2006 at the Southern Surgical Association meeting in Palm Beach, FL.
"High VEGF levels correspond with lymph node metastasis and worse prognosis in many cancers," Dr. Arafat says. "High levels of angiotensin II might mean high levels of VEGF and pancreatic cancer. We have a treatment to block it."
"We are continuing to analyze how angiotensin affects VEGF, and the signaling pathways involved," she says. Her team is looking at the effect of angiotensin on cell proliferation and programmed cell death, and would like to develop an animal model.
"Patients have chemotherapy and radiation sometimes before surgery," she says. "I would imagine this would be useful either for unresectable tumors or after surgical removal of the pancreatic cancer. It might be used in maintenance."
"These are well tested, safe drugs," Dr. Arafat notes, "so the translation of our work from the animal model to the clinical trial can be fast. This is very promising." Pancreatic cancer is the fourth leading cause of cancer death in the United States, with some 32,000 deaths a year. Only five percent of patients live at least one year after diagnosis.
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