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RLIP76 contributes to pancreatic cancer cell resistance to chemotherapy and radiation
Date:6/19/2012

LAKE TAHOE, Nev. Researchers at the City of Hope Comprehensive Cancer Center have not only identified a protein that allows pancreatic cancer cells to resist therapy but also developed a way to block it, according to results presented at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference, held here June 18-21.

"Cancer of the pancreas is notoriously difficult to treat because it usually presents at late stages due to minimal or nonspecific symptoms in the early stages. Thus, surgical treatment is either not possible or fails to cure most patients, resulting in a dismal prognosis 90 percent of patients are likely to die within a year," said Sanjay Awasthi, M.D., professor of medical oncology and therapeutics research, and diabetes, endocrinology and metabolism at City of Hope in Duarte, Calif.

One of the reasons that pancreatic cancer is so difficult to treat is that the tumor cells are largely resistant to the cell death caused by radiation and chemotherapy. Awasthi and colleagues have previously shown that the protein RLIP76 plays a key role in defending cells from other types of cancers from death caused by exposure to chemotherapy or radiation.

"RLIP76 works like an exhaust system," said Awasthi. "It pumps out the toxic chemicals that accumulate in the cancer cell as a result of chemo- or radiotherapy before they can cause cell death."

Now, Awasthi and colleagues have found that there is more RLIP76 in human pancreatic cancer cells than there is in normal human pancreatic cells. Depleting levels of RLIP76 killed human pancreatic cancer cells in culture and shrank established human pancreatic tumors in mice. Moreover, blocking RLIP76 or depleting levels of the protein dramatically enhanced the ability of radiation and the chemotherapeutic agent doxorubicin to destroy human pancreatic cells in culture.

"Pancreatic cancer patients are a special case of the parti
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Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

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