SAN DIEGO, April 18, 2016 /PRNewswire/ -- Polaris Group announced today that ADI-PEG 20, arginine deiminase formulated with polyethylene glycol, is a potential salvage therapy for BRAF inhibitor (BRAFi) resistant melanoma according to results generated by researchers from University of Miami, Taipei Medical University, and MD Anderson Cancer Center. The results will be presented at the American Association for Cancer Research's 2016 annual meeting in New Orleans, Louisiana.
In xenograft models of melanoma, ADI-PEG 20 treatment stopped tumor growth of BRAFi-resistant (BR) cells, while slowing tumor growth of the parental cells (BRAFi sensitive). Five BR melanoma cell lines derived from cells with known BRAF mutations were found to have very low levels of argininosuccinate synthetase (ASS1), the rate limiting enzyme in the arginine synthesis pathway in cells, and attenuated expression of AMPK-α 1, which governs autophagy and glucose uptake by cells. ASS1 deficiency caused the BR cells to rely exclusively on external supply of arginine, while low AMPK-α 1 led to attenuation of glucose uptake, increased reliance on amino acids, and impaired ability to handle nutritional stress. The dual deficiency of ASS1 and AMPK-α 1 renders the BR cells to be hypersensitive to treatment by ADI-PEG 20, which degrades arginine to citrulline. Immunohistochemistry staining confirmed low levels of ASS1 and AMPK-α 1 in xenograft tumor tissues and the tumor tissues from 10 BR patients. These findings also apply to tumor samples from patients who failed BRAF and MEK inhibitors, making ADI-PEG 20 a potential salvage therapy for BR patients.
Polaris Group is conducting clinical trials on ADI-PEG 20 for the treatment of multiple indications, including metastatic melanoma, malignant plural mesothelioma, and hepatocellular carcinoma.
"Although BRAFi and MEK inhibitor combination is highly effective in treating patients harboring BRAF V600E mutations, eventually tumors become resistant to BRAFi and these patients then relapse. We are excited about the discovery that ADI-PEG 20 can potentially become a treatment option for these patients," 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, a multinational biopharmaceutical drug company, specializes in the research and development of protein drugs to treat cancer and other debilitating diseases. Polaris Group is investigating ADI-PEG 20 as a treatment for a number of cancers, such as leukemia, lymphoma, melanoma, mesothelioma, non-small cell lung cancers, sarcoma, breast, ovarian, pancreatic cancer and hepatocellular carcinoma. In addition to the ADI-PEG 20 program, Polaris Group is researching and developing other biotherapeutic agents and is advancing a small molecule drug program that utilizes a rational structure-based approach to design novel compounds that inhibit the biological function of cancer-related protein targets.
For additional information please visit www.polarispharma.com.
SOURCE Polaris Group