imatinib
Imatinib mesylate (STI 571, Gleevec) is an inhibitor of the tyrosine kinases c-kit, PDGFR and the fusion protein BCR/ABL. Imatinib also blocks the stem cell factor SCF receptor or c-KIT loop.
Imatinib is a small-molecule ABL kinase inhibitor. It is a highly effective therapy for early-phase chronic myeloid leukaemia (CML), which has constitutively active ABL kinase activity owing to the expression of the BCR-ABL fusion protein.
Therapeutics
significant response in patients with chronic myelogenous leukemia and gastrointestinal stromal tumor (GIST)
Videos
Gleevec mechanism of Action
Reviews
O’hare T, Corbin AS, Druker BJ. Targeted CML therapy: controlling drug resistance, seeking cure. Curr Opin Genet Dev. 2006 Feb;16(1):92-9. PMID: #16343892#
Klein S, McCormick F, Levitzki A. Killing time for cancer cells. Nat Rev Cancer. 2005 Jul;5(7):573-80. PMID: #15965492#
Mohty M, Blaise D, Olive D, Gaugler B. Imatinib: the narrow line between immune tolerance and activation. Trends Mol Med. 2005 Sep;11(9):397-402. PMID: #16087402#
Hannah AL. Kinases as drug discovery targets in hematologic malignancies. Curr Mol Med. 2005 Nov;5(7):625-42. PMID: #16305489#
Savage DG, Antman KH. Imatinib mesylate—a new oral targeted therapy. N Engl J Med. 2002 Feb 28;346(9):683-93. PMID: #11870247#
References
Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005;353:172-187.
Apperley JF, Gardembas M, Melo JV, et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002;347:481-487.
David M, Cross NC, Burgstaller S, et al. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 2007;109:61-64.
Lichter P, Ward DC. Is non-isotopic in situ hybridization finally coming of age? Nature 1990;345:93-94.
Baccarani M, Cilloni D, Rondoni M, et al. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome: results of a multicenter prospective study. Haematologica 2007;92:1173-1179.
Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201-1214.
Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005;105:2640-2653. PMID: #15618470#
Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006;355:2408-2417.
Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001;293:876-880.
PDGFRA
Apperley JF, Gardembas M, Melo JV, et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002;347:481-487.
David M, Cross NC, Burgstaller S, et al. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 2007;109:61-64.
Baccarani M, Cilloni D, Rondoni M, et al. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome: results of a multicenter prospective study. Haematologica 2007;92:1173-1179.
Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201-1214.