Targeted therapy with MGCD0103?
The reseachers continue to look for signs that show which patients that will respond to the different drugs for MDS. Now they found a factor, Thrombospondin, that is upregulated in patients (only 2 patients so far) with clinical response on MGCD0103:
"2008 AACR, April 12-16, 2008
Abstract Number: 739
Induction of an anti-angiogenesis factor, Thrombospondin 1 (TSP-1), by a novel histone deacetylase inhibitor, MGCD0103, in human cancer cells in vitro and in vivo
Jianhong Liu, Claire Bonfils, Marja Dubay, Hannah Nguyen, Guillermo Garcia-Manero, Allen S. Yang, Selina Luger, Robert Martell, Jeffrey M. Besterman, Zuomei Li. MethylGene, Inc., Montréal, QC, Canada, MD Anderson Cancer Center, Houston, TX, Norris Comprehensive Cancer Center, Los Angeles, CA, Abramson Cancer Center, Philadelphia, PA
MGCD0103 is a novel non-hydroxamate histone deacetylase inhibitor which specifically targets HDAC1, 2, 3 and 11. Previously, we have shown that MGCD0103 has broad-spectrum antitumor activities in preclinical animal models and its preliminary clinical activity has been shown in multiple Phase II trials in patients with relapsed or refractory Hodgkin’s lymphoma or Non-Hodgkin lymphoma , high-risk myelodysplastic syndrome (MDS) and acute myologenous leukemia (AML)…
…Microarray analysis of peripheral blood mononuclear cells or bone marrow mononuclear cells from five AML patients, who were treated with MGCD0103 either alone or in combination with Vidaza, revealed that the upregulation of expression of TSP-1 in patients with clinical response (n=2) but not in those without response (n=3)…
…The utility of TSP-1 expression as a potential biomarker of MGCD0103 in clinical trials will be discussed."
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