ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP), a drug development company employing small molecule and synthetic biology approaches to cancer therapy, announced today that results from preclinical studies of darinaparsin (Zinapar® or ZIO-101), a novel organic arsenic, in prostate cancer were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place November 12-16 in San Francisco. In addition to Company authors, the studies included authors Joseph R. Bertino M.D. and Nitu Bansal Ph.D. from UMDNJ-The Cancer Institute of New Jersey.
The studies were designed to evaluate the effect of darinaparsin on the Hedgehog signaling pathway in prostate cancer. Aberrant hedgehog signaling has been implicated in a number of cancers due to its association with the transformation of adult stem cells into cancer stem cells. Data from the studies demonstrate that darinaparsin is a potent inhibitor of DU145 prostate cells, which inhibited prostate spheroid growth (IC50:2uM) and prostate stem cell colony formation. Western analysis showed that darinaparsin decreased levels of the transcription factor Gli2, a downstream effector of the activated Hedgehog pathway which is elevated in certain cancers. Further, combination studies with taxotere, a U.S. Food and Drug Administration-approved drug for the treatment of patients with advanced prostate cancer, showed synergistic cell destruction at high fixed doses of the drugs.
"We know from past research that arsenic trioxide inhibits growth in certain tumors through its activity against the Hedgehog pathway," commented Joseph Bertino, M.D., Associate Director and Chief Scientific Officer of the Cancer Institute of New Jersey, University Professor of Medicine and Pharmacology at UMDNJ-Robert Wood Johnson, former President of AACR and ASCO, and a member of ZIOPHARM's Medical Advisory Board. "Due to inorganic arsenic trioxide's severe cardiotoxicity and neurotoxicity profile, darinaparsin, an organic arsenic, was thought to be a far better treatment candidate and these studies encourage additional preclinical and clinical study, as a single agent and in combination."
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