Abstract
Chronic myeloid leukemia (CML) therapy has dramatically changed in the last decade due to the introduction of tyrosine kinase inhibitors (TKIs) - imatinib, nilotinib and dasatinib. Despite the significant prolongation of overall survival of CML patients there is still room for improvement. Approximately 20-25% of patients initially treated with imatinib will need alternative therapy, due to drug resistance which is often caused by the appearance of clones expressing mutant forms of BCR-ABL. Second generation TKIs dasatinib and nilotinib have shown promising results in imatinibresistant or intolerant CML patients, but are not active against CML clones with highly resistant T315I mutation. In recent years special attention is placed on small pool of leukemic stem cells which may contribute to the persistence of the leukemia. This article provides a review of preclinical and clinical data concerning the most promising new directions in CML treatment, with special emphasis on new drugs active in T315I mutation and compounds affecting leukemic stem cells.
Keywords: Chronic myeloid leukemia, leukemic stem cells, tyrosine kinase inhibitors, ponatinib, aurora kinase inhibitors, switch control inhibitors
Current Cancer Drug Targets
Title:Emerging Therapies in Chronic Myeloid Leukemia
Volume: 12 Issue: 5
Author(s): J. Gora-Tybor
Affiliation:
Keywords: Chronic myeloid leukemia, leukemic stem cells, tyrosine kinase inhibitors, ponatinib, aurora kinase inhibitors, switch control inhibitors
Abstract: Chronic myeloid leukemia (CML) therapy has dramatically changed in the last decade due to the introduction of tyrosine kinase inhibitors (TKIs) - imatinib, nilotinib and dasatinib. Despite the significant prolongation of overall survival of CML patients there is still room for improvement. Approximately 20-25% of patients initially treated with imatinib will need alternative therapy, due to drug resistance which is often caused by the appearance of clones expressing mutant forms of BCR-ABL. Second generation TKIs dasatinib and nilotinib have shown promising results in imatinibresistant or intolerant CML patients, but are not active against CML clones with highly resistant T315I mutation. In recent years special attention is placed on small pool of leukemic stem cells which may contribute to the persistence of the leukemia. This article provides a review of preclinical and clinical data concerning the most promising new directions in CML treatment, with special emphasis on new drugs active in T315I mutation and compounds affecting leukemic stem cells.
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Cite this article as:
Gora-Tybor J., Emerging Therapies in Chronic Myeloid Leukemia, Current Cancer Drug Targets 2012; 12 (5) . https://dx.doi.org/10.2174/156800912800673202
DOI https://dx.doi.org/10.2174/156800912800673202 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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