ADI-PEG 20 Radio-sensitizes Pancreatic Cancer Cells by Amplifying Early Endoplasmic Reticulum Stress

Wednesday, November 9, 2016 Cancer News
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SAN DIEGO, Nov. 8, 2016 /PRNewswire/ -- Polaris Group announced today that ADI-PEG 20, arginine deiminase formulated with

polyethylene glycol, can selectively enhance the effect of radiation in argininosuccinate synthetase (ASS1) deficient pancreatic tumors according to results presented by researchers from MD Anderson Cancer Center at the annual meeting of the American
Society for Radiation Oncology (ASTRO).

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The researchers reported that pre-treatment of ADI-PEG 20 sensitizes ASS1-deficient pancreatic tumor cells to radiation both in vitro and in vivo, resulting in enhanced cell killing in tissue culture and significantly delayed tumor growth in an animal model.  It is well known that radiation-associated cellular damage induces endoplasmic reticulum (ER) stress signals, which leads to disruption of cell cycle and apoptosis.  The results revealed that ADI-PEG 20 treatment increased the expression level of multiple proteins involved in ER stress induced by radiation, providing insight into the mechanism behind radio-sensitization by ADI-PEG 20. 

ADI-PEG 20 was designed to deplete arginine in the circulation. Tumor cells deficient in ASS1, a key enzyme in the arginine biosynthesis loop, are expected to be more sensitive to ADI-PEG 20 treatment.

"We are intrigued by the discovery that ADI-PEG 20 radio-sensitizes ASS1-deficient pancreatic cancer by upregulating proteins involved in ER stress, thereby expanding its mechanism of action and the scope of its potential use as an oncology therapeutic," said John Bomalaski, M.D., Executive Vice President of Medical Affairs at Polaris Pharmaceuticals, Inc.

About ADI-PEG 20

ADI-PEG 20 is a biologic being developed by Polaris Group to treat cancers, especially those carrying a major metabolic defect that renders such cancer cells, unlike normal cells, unable to internally synthesize arginine. Because arginine is one of the 20 amino acids that are essential for protein synthesis and survival of cells, it is believed these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI-PEG 20 is designed to deplete the external supply of arginine, which causes arginine-dependent cancer cells to die while leaving the patient's normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine dependency.

About Polaris Group

Polaris Group is a multinational biotechnology company specializing in the research and development of novel pharmaceuticals to treat cancer. The company's lead therapeutic, ADI-PEG 20, is a novel biologic in late stage clinical development. It has been tested in more than twenty clinical trials globally for a wide variety of cancers, including hepatocellular carcinoma, mesothelioma, pancreatic cancer, non-small cell lung cancer, melanoma, acute myeloid leukemia and others. As a fully integrated company, Polaris is engaged in applying protein structure-based drug design technology to develop novel drug candidates for cancers, conducting clinical studies at top-tier cancer centers worldwide, and manufacturing all clinical materials at its certified cGMP facilities in northern California.

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