o-(chloroacetylcarbamoyl)fumagillol and carboxyamido-triazole

Angiogenesis is the outgrowth of new vessels from pre-existing ones. Tumour growth and metastasis is dependent on angiogenesis and many stimulatory and inhibitory factors have been described which play an active role in this process. Inhibition of tumour neovasculature may be one strategy to inhibit tumour growth. Naturally occurring inhibitors of angiogenesis have been discovered and synthetic agents have been designed. Many of these inhibitors are currently being evaluated in clinical trials for the treatment of cancer. This review discusses the mechanism of action of these anti-angiogenics as well as a description of the clinical trials in which they are being evaluated.

Topics: Angiogenesis Inhibitors; Animals; Antibodies; Clinical Trials as Topic; Collagen; Cyclohexanes; Endostatins; Endothelial Growth Factors; Fatty Acids, Unsaturated; Humans; Interleukin-12; Lymphokines; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Neoplasms; O-(Chloroacetylcarbamoyl)fumagillol; Peptide Fragments; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; Receptors, Vitronectin; RNA, Catalytic; Sesquiterpenes; Suramin; Thalidomide; Triazoles; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Aberrant angiogenesis is closely involved in invasion/metastasis as well as enlargement of tumor. One recent highlight is to develop anti angiogenic drugs by targeting tumor angiogenesis. Here we describe how tumor angiogenesis is regulated and also recent topics related to angiogenic drug in clinical trials.

Topics: Antineoplastic Agents; Clinical Trials as Topic; Cyclohexanes; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; Hydroxamic Acids; Interferon-alpha; Interleukin-12; Neoplasms; Neovascularization, Pathologic; O-(Chloroacetylcarbamoyl)fumagillol; Phenylalanine; Platelet Factor 4; Polysaccharides, Bacterial; Sesquiterpenes; Thalidomide; Thiophenes; Triazines; Triazoles; Tumor Cells, Cultured

A new therapeutic strategy for treating metastasis in hepatocellular carcinoma (HCC) has entailed the use of antiangiogenic agents such as suramin, BB-94 (Batimastat), TNP-470, and carboxyamido-triazole (CAI, a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis). These agents have been used to treat metastatic model of HCC in nude mouse (LCI-D20 mouse model). The results of these studies are summarized in this paper with emphasis on the inhibitory effects of the drugs on tumour growth, angiogenesis, invasion and metastasis in LCI-D20 mouse models. The results suggest that all of the agents used can significantly inhibit tumour growth, angiogenesis, invasion and metastasis of human HCC in nude mouse models, and may be candidates for the control of recurrence and metastasis after HCC resection.

Topics: Animals; Antineoplastic Agents; Cell Division; Cyclohexanes; Liver Neoplasms, Experimental; Mice; Mice, Nude; Neoplasm Metastasis; Neovascularization, Pathologic; O-(Chloroacetylcarbamoyl)fumagillol; Phenylalanine; Sesquiterpenes; Suramin; Thiophenes; Triazoles