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Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia

The development of imatinib for the treatment of chronic myeloid leukemia (CML) has proven to be an example of medical success in the era of targeted therapy. However, imatinib resistance or intolerance occurs in a substantial number of patients. Additionally, patients who have progressed beyond the...

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Detalles Bibliográficos
Autores principales: Ramchandren, Radhakrishnan, Schiffer, Charles A
Formato: Texto
Lenguaje:English
Publicado: Dove Medical Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726068/
https://www.ncbi.nlm.nih.gov/pubmed/19707409
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author Ramchandren, Radhakrishnan
Schiffer, Charles A
author_facet Ramchandren, Radhakrishnan
Schiffer, Charles A
author_sort Ramchandren, Radhakrishnan
collection PubMed
description The development of imatinib for the treatment of chronic myeloid leukemia (CML) has proven to be an example of medical success in the era of targeted therapy. However, imatinib resistance or intolerance occurs in a substantial number of patients. Additionally, patients who have progressed beyond the chronic phase of CML do relatively poorly with imatinib therapy. Mechanisms of imatinib resistance include BCR-ABL point mutations resulting in decreased imatinib binding, as well as mutation-independent causes of resistance such as SRC family kinase dysregulation, BCR-ABL gene amplification, drug influx/efflux mechanisms and other poorly understood processes. The options for therapy in these patients include stem cell transplantation, imatinib dose escalation as well as the use of second-generation tyrosine kinase inhibitors. Dasatinib is a second-generation multi-kinase inhibitor with several theoretical and mechanistic advantages over imatinib. Moreover, several studies have evaluated dasatinib in patients who have progressed on imatinib therapy with encouraging results. Other novel agents such as mTOR inhibitors, bosutinib and INNO 406 have also shown promise in this setting. Although treatment options have increased, the choice of second-line therapy in patients with CML is influenced by concerns surrounding the duration of response as well as toxicity. Consequently, there is no agreed upon optimal second-line agent. This paper reviews the current data and attempts to address these issues.
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spelling pubmed-27260682009-08-25 Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia Ramchandren, Radhakrishnan Schiffer, Charles A Biologics Original Research The development of imatinib for the treatment of chronic myeloid leukemia (CML) has proven to be an example of medical success in the era of targeted therapy. However, imatinib resistance or intolerance occurs in a substantial number of patients. Additionally, patients who have progressed beyond the chronic phase of CML do relatively poorly with imatinib therapy. Mechanisms of imatinib resistance include BCR-ABL point mutations resulting in decreased imatinib binding, as well as mutation-independent causes of resistance such as SRC family kinase dysregulation, BCR-ABL gene amplification, drug influx/efflux mechanisms and other poorly understood processes. The options for therapy in these patients include stem cell transplantation, imatinib dose escalation as well as the use of second-generation tyrosine kinase inhibitors. Dasatinib is a second-generation multi-kinase inhibitor with several theoretical and mechanistic advantages over imatinib. Moreover, several studies have evaluated dasatinib in patients who have progressed on imatinib therapy with encouraging results. Other novel agents such as mTOR inhibitors, bosutinib and INNO 406 have also shown promise in this setting. Although treatment options have increased, the choice of second-line therapy in patients with CML is influenced by concerns surrounding the duration of response as well as toxicity. Consequently, there is no agreed upon optimal second-line agent. This paper reviews the current data and attempts to address these issues. Dove Medical Press 2009 2009-07-13 /pmc/articles/PMC2726068/ /pubmed/19707409 Text en © 2009 Ramchandren and Schiffer, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Ramchandren, Radhakrishnan
Schiffer, Charles A
Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_full Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_fullStr Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_full_unstemmed Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_short Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_sort dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726068/
https://www.ncbi.nlm.nih.gov/pubmed/19707409
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