ABT-510

ABT-510 is a molecular therapeutic drug used to treat cancer. According to the "Journal of Clinical Oncology", ABT-510 is a "subcutaneously (SC) administered nonapeptide thrombospondin analogue in phase 2 clinical development for treatment of advanced malignancies." [Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 3080] [ [http://www.jamesline.com/cancertypes/glossary/index.cfm?action=Display&ID=367468&Letter=A NCI: ABT-510 ] ]

ABT-510 is a new Abbott compound showing promise as an angiogenesis inhibitor or anti-angiogenic agent, meaning it works by stopping the growth of new blood vessels. [ [http://www.jamesline.com/cancertypes/glossary/index.cfm?action=Display&ID=367468&Letter=A NCI: ABT-510 ] ] This Thrombospondin 1 mimetic works through CD36 and has been shown to block angiogenesis in vitro and in vivo and to slow tumor growth in mice.

ABT-510 was shown to be effective in both xenograft models [Yang Q, Tian Y, Liu S, Zeine R, Chlenski A, Salwen HR, Henkin J, Cohn SL. (2007) Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Cancer Res 67(4):1716-24] and in a study of companion dogs with spontaneous tumors. Not only were objective responses observed after 60 days, but a decrease in levels of circulating endothelial cells was also found [Rusk A, McKeegan E, Haviv F, Majest S, Henkin J, Khanna C. (2006) Preclinical evaluation of antiangiogenic thrombospondin-1 peptide mimetics, ABT-526 and ABT-510, in companion dogs with naturally occurring cancers. Clin Cancer Res 12(24):7444-55] .

In human studies, ABT-510 was found to be safe and have efficacy in phase I trials in combination regimens [Gietema JA, Hoekstra R, de Vos FY, Uges DR, van der Gaast A, Groen HJ, Loos WJ, Knight RA, Carr RA, Humerickhouse RA, Eskens FA. (2006) A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors. Ann Oncol 17(8):1320-7] [Hoekstra R, de Vos FY, Eskens FA, de Vries EG, Uges DR, Knight R, Carr RA, Humerickhouse R, Verweij J, Gietema JA. (2006) Phase I study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with 5-fluorouracil and leucovorin: a safe combination. Eur J Cancer 42(4):467-72] , and as a single agent, where its use was associated with a decrease in bFGF levels and stable disease in six patients for at least six months [Hoekstra R, de Vos FY, Eskens FA, Gietema JA, van der Gaast A, Groen HJ, Knight RA, Carr RA, Humerickhouse RA, Verweij J, de Vries EG. (2005) Phase I safety, pharmacokinetic, and pharmacodynamic study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 in patients with advanced cancer. J Clin Oncol 23(22):5188-97] .

The combination of bevacizumab and ABT-510 has been shown (in a phase I study) to be effective in promoting stable disease in 44% of patients with advanced solid tumors [Uronis HE, Bendell J, Blobe G, Morse M, Geier D, Nixon A, Howard L, Evans D, Li H, Hurwitz H. (2007) A phase I study of bevacizumab (BV) plus ABT-510 in patients with advanced solid tumors. ASCO Proceedings Abstract 3541] .

Unfortunately, the recent phase II study of ABT-510 for treatment of metastatic melanoma failed to reach its primary endpoint resulting in early termination of the study. Only three out of twenty-one patients reached the primary endpoint of progression-free survival at 18 weeks, but these three patients remained progression-free for 21, 34, and 42 weeks. However, biomarker data collected during this study showed a decrease in VEGF-C, circulating endothelial cells, and CD146 and CD34/133 counts, and a maximum tolerated dose has still not been established. Further study could consider a higher dose and/or combination treatment [Markovic SN, Suman VJ, Rao RA, Ingle JN, Kaur JS, Erickson LA, Pitot HC, Croghan GA, McWilliams RR, Merchan J, Kottschade LA, Nevala WK, Uhl CB, Allred J, Creagan ET. (2007) A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of metastatic melanoma. Am J Clin Oncol. 30(3):303-9] .

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