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Polaris Group Lead Therapeutic Candidate ADI-PEG 20 Demonstrates Potential Anticancer Activity in Various Metastatic Sarcomas and Bladder Cancers That Are Deficient in Key Metabolic Protein, and Enhanced Effects with Combination Therapy in Melanoma
Date:6/12/2012

SAN DIEGO, June 12, 2012 /PRNewswire/ -- Scientists from numerous institutions reported at the 2012 annual American Association for Cancer Research meeting, results from preclinical studies which showed that certain sarcomas and bladder cancers are more likely to respond to treatment with ADI-PEG 20 pegylated arginine deiminase) if they are deficient in the enzyme, argininosuccinate synthetase (ASS). This enzyme plays an important role in the synthesis of the amino acid arginine required for proteins in cell growth and function. Its deficiency in certain cancer cells requires these cells to obtain arginine from the circulation in order to survive.  ADI-PEG 20 destroys arginine in circulation thereby preventing the cancers from growing. In addition, others showed that activation of a signaling pathway up regulates ASS, and that combination inhibition of that pathway together with ADI-PEG 20 overcame resistance to ADI-PEG 20 in melanoma, suggesting that ADI-PEG 20 combination therapy may be even more potent than mono-therapy.

Sowers et al from NY (Albert Einstein College of Medicine and Children's Hospital at Montefiore) (abstract No.1692) obtained osteosarcoma cell lines from primary patient tumors. Of 171 tissue slides stained with ASS antibody, 141 (66.7%) of samples had absent or negligible staining, 25.7% showed moderate staining and 7.6% showed strong staining. Results from cell cytotoxicity studies comparing ADI-PEG 20 treatment of ASS deficient cell lines and ASS positive cells showed a correlation of cell toxicity with decreased levels of ASS staining. Further studies with ADI-PEG 20 using human osteosarcoma in mouse xenograft models are ongoing.

Weich et al from Washington University in St. Louis, MO and The Cleveland Clinic, Cleveland, OH (abstract No.5629) performed ASS antibody staining analysis with sarcoma tissue samples from 701 patients and demonstrated that >85% (619 of 701) of the sarcomas did not express
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