ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) announced today important new preclinical data on the efficacy of darinaparsin (ZinaparTM, or ZIO-101) in various solid tumor models delivered at the EORTC-NCI-AACR International Symposium on Molecular Targets and Cancer Therapeutics being held in Berlin, Germany. Lead author, Susan Knox, M.D., Ph.D., Associate Professor, Department of Radiation Oncology and Member of BIO-X and Advising Dean at Stanford University School of Medicine, presented the abstract, "Darinaparsin (ZIO-101) is a novel cytotoxic and radiosensitizing anti-cancer agent".
“Darinaparsin (ZIO-101) is a novel cytotoxic and radiosensitizing anti-cancer agent”
The preclinical work was designed to study darinaparsin's cytotoxic and radiosensitizing effects against different solid tumor cell lines under both normoxic (NO) and hypoxic (HO) conditions. Hypoxia is an important condition in the microenvironment of solid tumor cells which creates resistance to cytotoxic drugs and radiation and causes cancer stem cells to re-grow the tumor. In these studies, hormone independent prostate cancer, pancreatic cancer, cervical cancer, and glioblastoma cell lines were treated with darinaparsin at concentrations ranging from 0.01 to 10 uM under either NO or HO conditions and irradiated with doses of 0 - 5 Gy. Results showed that darinaparsin is a potent cytotoxin under both NO and HO conditions and under HO when cells are resistant to radiation. Significant radiation enhancement was also observed in clonogenic assays under HO at clinically relevant doses, raising the potential for synergistic and dose-sparing radiation therapy. Darinaparsin's cytotoxic and radiation enhancing modes of action are distinct from other cytotoxic agents and were not dependent on generation of reactive oxygen species and DNA damage under HO.
"Darinaparsin's multiple mechanisms of action and potency provide for cytotoxicity and radiosensitization in a variety of tumor cell lines and environments," commented Dr. Knox. "This activity suggests a broad potential applicability for darinaparsin in the treatment of chemo- and radio-resistant solid tumors, with near term translational potential."
In September, ZIOPHARM announced that darinaparsin was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of peripheral T-cell Lymphoma (PTCL). Intravenous darinaparsin has demonstrated favorable results in a Phase II trial in lymphoma and particularly for PTCL. With a Phase I trial using the oral form ongoing in solid tumors and the results presented today, clinical development is expected to proceed in both PTCL and solid tumors.
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