TY - JOUR
T1 - Tyrosine kinase inhibitors
T2 - The first decade
AU - Agrawal, Meetu
AU - Garg, Ravin J.
AU - Cortes, Jorge
AU - Quintás-Cardama, Alfonso
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2010/4
Y1 - 2010/4
N2 - The treatment of chronic myeloid leukemia (CML) drastically changed with the introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), in 1998. By directly targeting this leukemogenic protein kinase, imatinib affords patients with CML sustained chromosomal remissions, which translate into prolonged survival. However, there has been concern over the emergence of resistance to imatinib, and some patients fail to respond or are intolerant of imatinib therapy because of untoward toxicity. This has spurred interest in developing novel TKIs to overcome the mechanisms of resistance that lead to treatment failure-most importantly, Bcr-Abl1 kinase domain mutations. Two of these second-generation TKIs, nilotinib and dasatinib, are approved worldwide for the treatment of CML after imatinib failure or intolerance.Although these agents are active, they fail in many patients because of the development of highly resistant mutations such as the T315I, against which several novel agents are currently being tested in clinical trials. This review provides an account of the progress made in the field of TKI therapy for CML over the past decade.
AB - The treatment of chronic myeloid leukemia (CML) drastically changed with the introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), in 1998. By directly targeting this leukemogenic protein kinase, imatinib affords patients with CML sustained chromosomal remissions, which translate into prolonged survival. However, there has been concern over the emergence of resistance to imatinib, and some patients fail to respond or are intolerant of imatinib therapy because of untoward toxicity. This has spurred interest in developing novel TKIs to overcome the mechanisms of resistance that lead to treatment failure-most importantly, Bcr-Abl1 kinase domain mutations. Two of these second-generation TKIs, nilotinib and dasatinib, are approved worldwide for the treatment of CML after imatinib failure or intolerance.Although these agents are active, they fail in many patients because of the development of highly resistant mutations such as the T315I, against which several novel agents are currently being tested in clinical trials. This review provides an account of the progress made in the field of TKI therapy for CML over the past decade.
KW - CML
KW - Cancer therapy
KW - Chronic myeloid leukemia
KW - Dasatanib
KW - Imatinib
KW - Nilotinib
KW - TKIs
KW - Tyrosine kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=77954623320&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954623320&partnerID=8YFLogxK
U2 - 10.1007/s11899-010-0045-y
DO - 10.1007/s11899-010-0045-y
M3 - Review article
C2 - 20425399
AN - SCOPUS:77954623320
VL - 5
SP - 70
EP - 80
JO - Current Hematologic Malignancy Reports
JF - Current Hematologic Malignancy Reports
SN - 1558-8211
IS - 2
ER -