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New targeted therapies for chronic myelogenous leukemia: opportunities to overcome imatinib resistance.
- Source :
-
Seminars in hematology [Semin Hematol] 2007 Jan; Vol. 44 (1 Suppl 1), pp. S25-31. - Publication Year :
- 2007
-
Abstract
- The advent of tyrosine kinase inhibitors (TKIs) has ushered in a new era in the management of chronic myelogenous leukemia (CML). Imatinib, the first TKI to be approved for the treatment of CML and the current standard first-line therapy, has significantly improved the prognosis of patients with CML. Nevertheless, a minority of patients in chronic-phase CML and even more patients with advanced-phase disease demonstrate resistance to imatinib or develop resistance during treatment. In 40% to 50% of cases, this is attributed to the development of mutations that impair the ability of imatinib to bind to and inhibit the constitutively active Bcr-Abl kinase. Consequently, researchers have developed novel, more potent TKIs that can overcome not only Bcr-Abl-dependent mechanisms of resistance, but also those that are Bcr-Abl-independent. These include: dasatinib, a potent dual Bcr-Abl and Src inhibitor; nilotinib, a selective, potent Bcr-Abl inhibitor; bosutinib (SKI-606) and INNO-406 (NS-187), which are both Src-Abl inhibitors; and others. Combination therapy is also being explored concurrently using agents that affect a variety of oncogenic pathways and immune modulation. Herein, we review some of these strategies, particularly those for which clinical data are currently available.
- Subjects :
- Adaptor Proteins, Signal Transducing antagonists & inhibitors
Aniline Compounds pharmacology
Benzamides
Cancer Vaccines
Clinical Trials as Topic
Dasatinib
Drug Resistance, Neoplasm drug effects
Drug Resistance, Neoplasm physiology
Fusion Proteins, bcr-abl genetics
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive physiopathology
Nitriles pharmacology
Piperazines pharmacology
Protein Kinase Inhibitors pharmacology
Pyrimidines pharmacology
Quinolines pharmacology
Thiazoles pharmacology
Fusion Proteins, bcr-abl drug effects
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Protein-Tyrosine Kinases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0037-1963
- Volume :
- 44
- Issue :
- 1 Suppl 1
- Database :
- MEDLINE
- Journal :
- Seminars in hematology
- Publication Type :
- Academic Journal
- Accession number :
- 17292738
- Full Text :
- https://doi.org/10.1053/j.seminhematol.2006.12.003