(ChemotherapyAdvisor) – The multifunctional cell membrane protein RLIP76 represents a mechanistically significant target for developing effective interventions for pancreatic cancers resistant to chemotherapy and radiation, according to results of a study presented June 19 at the American Association for Cancer Research’s Pancreatic Cancer: Progress and Challenges conference, Lake Tahoe, NV.

The study determined whether targeted depletion of RLIP76, expression of which is elevated in pancreatic cancer cells, represented an effective antineoplastic therapy that could overcome chemotherapy and radiation resistance in pancreatic cancer and whether the PI3K/AKT signaling pathway is affected. Previously, in-vitro studies have indicated a role for PI3K/AKT as mechanisms of apoptosis resistance in pancreatic cancer, and inhibition of RLIP76 has been shown to antagonize both PI3K and AKT in other cancers, noted Sanjay Awasthi, MD, of City of Hope Comprehensive Cancer Center, Duarte, CA.

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The investigators found RLIP76 depletion caused marked and sustained regression of established human BxPC-3 pancreatic cancer tumors in a nude mouse xenograft model, and confirmed the ability of RLIP76 to mediate drug and radiation resistance.

“Results of signaling studies are consistent with an encompassing model for the role of RLIP76 in regulating the levels of fundamental proteins like PI3K, AKT, E-cadherin, CDK4, Bcl2 and PCNA,” Leake concluded.

According to Dr. Awasthi, one added benefit to depleting levels of RLIP76 in the mice with established tumors was a decrease in blood glucose, cholesterol, and triglycerides. “These findings indicate that it might be possible to develop a single class of medications that have potent antidiabetic and anticancer effects,” he said.