New Pancreatic Cancer Study Results From M.T. Mueller Et Al Described

NewsRx.com

October 8, 2009

"Pancreatic cancers contain exclusively tumorigenic cancer stem cells (CSCs), which are highly resistant to chemotherapy, resulting in a relative increase in CSC numbers during gemcitabine treatment. Signaling through sonic hedgehog and mammalian target of rapamycin (mTOR), respectively, may be essential for CSC self-renewal and could represent putative targets for novel treatment modalities," scientists in Madrid, Spain report.

"We used in vitro and in vivo models of pancreatic cancer to examine the effects of sonic hedgehog inhibition (cyclopamine/CUR199691) and mTOR blockade (rapamycin) on the tumorigenic CSC population. Surprisingly, neither cyclopamine nor rapamycin alone or as supplements to chemotherapy were capable of effectivety diminishing the CSC pool. Only the combined inhibition of both pathways together with chemotherapy reduced the number of CSCs to virtually undetectable levels in vitro and in vivo. Most importantly, in vivo administration of this triple combination in mice with established patient-derived pancreatic tumors was reasonably tolerated and translated into significantly prolonged long-term survival. The combined blockade of sonic hedgehog and mTOR signaling together with standard chemotherapy is capable of eliminating pancreatic CSCs," wrote M.T. Mueller and colleagues.

The researchers concluded: "Further preclinical investigation of this promising approach may lead to the development of a novel therapeutic strategy to improve the devastating prognosis of patients with pancreatic cancer."

Mueller and colleagues published their study in Gastroenterology (Combined Targeted Treatment to Eliminate Tumorigenic Cancer Stem Cells in Human Pancreatic Cancer. Gastroenterology, 2009;137(3):1102-1113).

For more information, contact C. Heeschen, Spanish National Cancer Research Center CNIO, Clinic Research Program, Stem Cells & Cancer Unit, Madrid, Spain.

Publisher contact information for the journal Gastroenterology is: W B Saunders Co-Elsevier Inc., 1600 John F Kennedy Boulevard, Ste. 1800, Philadelphia, PA 19103-2899, USA.

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