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Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia
The BCR-ABL kinase inhibitor imatinib has shown significant efficacy in chronic myeloid leukemia (CML) and is the standard front-line therapy for patients in chronic phase. However, a substantial number of patients are either primarily refractory or acquire resistance to imatinib. While a number of...
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Formato: | Texto |
Lenguaje: | English |
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Informa Healthcare
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430171/ https://www.ncbi.nlm.nih.gov/pubmed/18203007 http://dx.doi.org/10.1080/10428190701713689 |
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author | Li, Shaoguang |
author_facet | Li, Shaoguang |
author_sort | Li, Shaoguang |
collection | PubMed |
description | The BCR-ABL kinase inhibitor imatinib has shown significant efficacy in chronic myeloid leukemia (CML) and is the standard front-line therapy for patients in chronic phase. However, a substantial number of patients are either primarily refractory or acquire resistance to imatinib. While a number of mechanisms are known to confer resistance to imatinib, increasing evidence has demonstrated a role for BCR-ABL–independent pathways. The Src-family kinases (SFKs) are one such pathway and have been implicated in imatinib resistance. Additionally, these kinases are key to the progression of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The dual SFK/BCR-ABL inhibitor dasatinib is now clinically available and has markedly greater potency compared with imatinib against native BCR-ABL and the majority of imatinib resistant BCR-ABL mutants. Therefore, this agent, as well as other dual SFK/BCR-ABL inhibitors under development, could provide added therapeutic advantages by overcoming both BCR-ABL– dependent (i.e., BCR-ABL mutations) and – independent forms of imatinib resistance and delaying transition to advanced phase disease. In this review, we discuss the preclinical and clinical evidence demonstrating the involvement of SFKs in imatinib resistance and the progression of CML and Ph+ ALL, as well as the potential role of dual SFK/BCR-ABL inhibition in the management of these diseases. |
format | Text |
id | pubmed-2430171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Informa Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-24301712008-06-19 Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia Li, Shaoguang Leuk Lymphoma Review The BCR-ABL kinase inhibitor imatinib has shown significant efficacy in chronic myeloid leukemia (CML) and is the standard front-line therapy for patients in chronic phase. However, a substantial number of patients are either primarily refractory or acquire resistance to imatinib. While a number of mechanisms are known to confer resistance to imatinib, increasing evidence has demonstrated a role for BCR-ABL–independent pathways. The Src-family kinases (SFKs) are one such pathway and have been implicated in imatinib resistance. Additionally, these kinases are key to the progression of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The dual SFK/BCR-ABL inhibitor dasatinib is now clinically available and has markedly greater potency compared with imatinib against native BCR-ABL and the majority of imatinib resistant BCR-ABL mutants. Therefore, this agent, as well as other dual SFK/BCR-ABL inhibitors under development, could provide added therapeutic advantages by overcoming both BCR-ABL– dependent (i.e., BCR-ABL mutations) and – independent forms of imatinib resistance and delaying transition to advanced phase disease. In this review, we discuss the preclinical and clinical evidence demonstrating the involvement of SFKs in imatinib resistance and the progression of CML and Ph+ ALL, as well as the potential role of dual SFK/BCR-ABL inhibition in the management of these diseases. Informa Healthcare 2008-01 2008-01-17 /pmc/articles/PMC2430171/ /pubmed/18203007 http://dx.doi.org/10.1080/10428190701713689 Text en © 2008 Informa UK Ltd http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Li, Shaoguang Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia |
title | Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia |
title_full | Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia |
title_fullStr | Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia |
title_full_unstemmed | Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia |
title_short | Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia |
title_sort | src-family kinases in the development and therapy of philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430171/ https://www.ncbi.nlm.nih.gov/pubmed/18203007 http://dx.doi.org/10.1080/10428190701713689 |
work_keys_str_mv | AT lishaoguang srcfamilykinasesinthedevelopmentandtherapyofphiladelphiachromosomepositivechronicmyeloidleukemiaandacutelymphoblasticleukemia |