Vascular Targeting Agents as Cancer Therapeutics

作者: Philip E. Thorpe

DOI: 10.1158/1078-0432.CCR-0642-03

关键词:

摘要: Vascular targeting agents (VTAs) for the treatment of cancer are designed to cause a rapid and selective shutdown blood vessels tumors. Unlike antiangiogenic drugs that inhibit formation new vessels, VTAs occlude pre-existing tumors tumor cell death from ischemia extensive hemorrhagic necrosis. Tumor selectivity is conferred by differences in pathophysiology versus normal tissue (e.g., increased proliferation fragility, up-regulated proteins). can kill indirectly cells resistant conventional antiproliferative therapies, i.e., areas distant where drug penetration poor, hypoxia lead radiation resistance. expected show greatest therapeutic benefit as part combined modality regimens. Preclinical studies have shown VTA-induced enhancement effects chemotherapeutic agents, radiation, hyperthermia, radioimmunotherapy, agents. There broadly two types VTAs, small molecules ligand-based, which grouped together, because they both acute vascular leading massive The include microtubulin destabilizing drugs, combretastatin A-4 disodium phosphate, ZD6126, AVE8062, Oxi 4503, flavonoid, DMXAA. Ligand-based use antibodies, peptides, or growth factors bind selectively target with vessels. ligand-based fusion proteins endothelial factor linked plant toxin gelonin), immunotoxins monoclonal antibodies endoglin conjugated ricin A), cytokines, liposomally encapsulated gene therapy approaches. Combretastatin DMXAA undergoing clinical evaluation. Phase I monotherapy tolerated some demonstration single agent efficacy. Because efficacy when used results II combination eagerly awaited.

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