Selective inhibition of proliferating endothelial cells: A phase I study of the novel organoarsenical compound GSAO in patients with advanced solid tumors
| Autor: | Andrew R Clamp, L. McGuigan, Y. K. Zee, Mark R. Middleton, Gordon C Jayson, Philip J. Hogg, A. Jackson, Geoffrey J. M. Parker, Al Harris, Gireesh C Kumaran |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 28:TPS167-TPS167 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | TPS167 Background: 4-(N-(S- glutathionylacetyl)amino)phenylarsonous acid (GSAO) is a new water-soluble organoarsenical that selectively inhibits proliferating endothelial cells (EC) in vitro and angiogenesis and tumor growth in human tumor xenografts in vivo. The prodrug GSAO is cleaved by γ-glutamyl transpeptidase (γGT), which is commonly overexpressed on the surface of cancer cells before entering surrounding ECs where it interacts with its mitochondrial target, adenine nucleotide translocase (ANT). ECs are specifically sensitive to GSAO due to their low expression of the multidrug resistance-associated proteins 1 and 2 (MRP 1/2), whereas cancer cells are less sensitive because of higher MRP 1/2 expression. This phase I dose escalation study aims to establish the maximum tolerated dose (MTD) of GSAO, to assess the safety and toxicity profile and to identify the dose limiting toxicity (DLT). Methods: Patients with solid cancers refractory to standard therapy are eligible for the study. Three patients are... |
| Databáze: | OpenAIRE |
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