Resistance to imatinib mesylate in chronic myeloid leukaemia
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- 作者：Junia V. Melo ; Charles Chuah
- 关键词：Chronic myeloid leukaemia ; Imatinib mesylate ; Drug resistance
- 刊名：Cancer Letters
- 出版年：2007
- 出版时间：8 May 2007
- 年：2007
- 卷：249
- 期：2
- 页码：121-132
- 全文大小：415 K
文摘
Despite the remarkable results achieved with imatinib for the treatment of chronic myeloid leukaemia, the emergence of resistance to this tyrosine kinase inhibitor has become a significant problem. Much progress has been recently made in elucidating the mechanisms which underlie imatinib resistance. The most common cause of such drug resistance is the selection of leukaemic clones with point mutations in the Abl kinase domain leading to amino acid substitutions which prevent the appropriate binding of the drug. Other mechanisms include genomic amplification of BCR-ABL and modulation of drug efflux or influx transporters. There is a pressing need, therefore, to develop and test novel drugs and strategies. Two such compounds are now being explored in clinical trials. This review will describe the molecular basis of imatinib-resistance and strategies to overcome resistance.