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Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system and has been treated with the drug Imatinib relatively successfully. Drug resistance, acquired by mutations, is an obstacle to success. Two additional drugs are now considered and could be combined with Imatinib to prevent resist...

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Detalles Bibliográficos
Autores principales: Komarova, Natalia L., Katouli, Allen A., Wodarz, Dominik
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635955/
https://www.ncbi.nlm.nih.gov/pubmed/19204794
http://dx.doi.org/10.1371/journal.pone.0004423
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author Komarova, Natalia L.
Katouli, Allen A.
Wodarz, Dominik
author_facet Komarova, Natalia L.
Katouli, Allen A.
Wodarz, Dominik
author_sort Komarova, Natalia L.
collection PubMed
description Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system and has been treated with the drug Imatinib relatively successfully. Drug resistance, acquired by mutations, is an obstacle to success. Two additional drugs are now considered and could be combined with Imatinib to prevent resistance, Dasatinib and Nilotinib. While most mutations conferring resistance to one drug do not confer resistance to the other drugs, there is one mutation (T315I) that induces resistance against all three drugs. Using computational methods, the combination of two drugs is found to increase the probability of treatment success despite this cross-resistance. Combining more than two drugs, however, does not provide further advantages. We also explore possible combination therapies using drugs currently under development. We conclude that among the targeted drugs currently available for the treamtent of CML, only the two most effective ones should be used in combination for the prevention of drug resistance.
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spelling pubmed-26359552009-02-10 Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia Komarova, Natalia L. Katouli, Allen A. Wodarz, Dominik PLoS One Research Article Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system and has been treated with the drug Imatinib relatively successfully. Drug resistance, acquired by mutations, is an obstacle to success. Two additional drugs are now considered and could be combined with Imatinib to prevent resistance, Dasatinib and Nilotinib. While most mutations conferring resistance to one drug do not confer resistance to the other drugs, there is one mutation (T315I) that induces resistance against all three drugs. Using computational methods, the combination of two drugs is found to increase the probability of treatment success despite this cross-resistance. Combining more than two drugs, however, does not provide further advantages. We also explore possible combination therapies using drugs currently under development. We conclude that among the targeted drugs currently available for the treamtent of CML, only the two most effective ones should be used in combination for the prevention of drug resistance. Public Library of Science 2009-02-10 /pmc/articles/PMC2635955/ /pubmed/19204794 http://dx.doi.org/10.1371/journal.pone.0004423 Text en Komarova et al. http://creativecommons.org/licenses/by/4.0/ 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 author and source are properly credited.
spellingShingle Research Article
Komarova, Natalia L.
Katouli, Allen A.
Wodarz, Dominik
Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia
title Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia
title_full Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia
title_fullStr Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia
title_full_unstemmed Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia
title_short Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia
title_sort combination of two but not three current targeted drugs can improve therapy of chronic myeloid leukemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635955/
https://www.ncbi.nlm.nih.gov/pubmed/19204794
http://dx.doi.org/10.1371/journal.pone.0004423
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