Combination of two but not three current targeted drugs can improve therapy of chronic myeloid leukemia.
Combination of two but not three current targeted drugs can improve therapy of chronic myeloid leukemia.
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DOI：
10.1371/journal.pone.0004423
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Wodarz D
中科院分区：
文献类型：
--
作者：
Komarova NL;Katouli AA;Wodarz D
慢性粒细胞白血病（CML）是一种造血系统癌症，用伊马替尼药物治疗相对成功。通过突变获得的耐药性是成功的障碍。现在正在考虑另外两种药物，达沙替尼和尼罗替尼，可以与伊马替尼联合使用以预防耐药性。虽然大多数赋予一种药物耐药性的突变不会赋予对其他药物的耐药性，但有一种突变 (T315I) 会诱导对所有三种药物的耐药性。使用计算方法，发现两种药物的组合可以增加治疗成功的可能性，尽管存在交叉耐药性。然而，组合两种以上的药物并不能提供进一步的优势。我们还探索使用目前正在开发的药物的可能的联合疗法。我们的结论是，在目前治疗CML的靶向药物中，只有两种最有效的药物才能联合使用，以预防耐药性。
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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影响因子：
50.3
作者：
Shannon, KM
通讯作者：
Shannon, KM
DOI：
10.1073/pnas.0504952102
发表时间：
2005-08-02
影响因子：
11.1
作者：
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DOI：
10.1073/pnas.0501870102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Komarova, NL;Wodarz, D
通讯作者：
Wodarz, D
影响因子：
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作者：
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通讯作者：
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