Chronic myeloid leukemia: advances in understanding disease biology and mechanisms of resistance to tyrosine kinase inhibitors.
Chronic myeloid leukemia: advances in understanding disease biology and mechanisms of resistance to tyrosine kinase inhibitors.
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DOI：
10.1007/s11899-015-0248-3
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发表时间：
2015-06
影响因子：
2.9
通讯作者：
O'Hare, Thomas
中科院分区：
文献类型：
--
作者：
Eide, Christopher A.;O'Hare, Thomas
关键词：
酪氨酸激酶抑制剂（TKI）治疗慢性粒细胞白血病（CML）的成功实施仍然是癌症分子靶向治疗的旗舰。这篇重点综述强调了CML潜在生物学的关键要素，并总结了导致TKI耐药的分子机制：基于BCR-ABL 1突变的耐药和通过旁路途径激活的治疗逃避，尽管BCR-ABL 1酪氨酸激酶活性受到抑制。我们将注意力集中在这些问题的最新表现上，包括泛TKI耐药BCR-ABL 1复合突变体的出现，替代途径的识别和治疗靶向的新策略，以及令人兴奋的、有争议的停止TKI治疗的话题，导致一部分患者持久的无治疗缓解。我们对费城染色体阳性（Ph阳性）白血病的生物学和BCR-ABL 1 TKI耐药机制的进一步了解将使患者受益，并为其他癌症的类似发现提供蓝图。
The successful implementation of tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML) remains a flagship for molecularly targeted therapy in cancer. This focused review highlights critical elements of the underlying biology of CML and provides a summary of the molecular mechanisms that lead to TKI resistance: BCR-ABL1 mutation-based resistance and therapy escape through alternative pathway activation despite inhibition of BCR-ABL1 tyrosine kinase activity. We direct attention to the most current manifestations of these issues, including emergence of pan-TKI-resistant BCR-ABL1 compound mutants, new strategies for identification and therapeutic targeting of alternative pathways, and the exciting, controversial topic of cessation of TKI therapy leading to durable treatment-free remissions for a subset of patients. Further gains in our understanding of the biology of Philadelphia chromosome-positive (Ph-positive) leukemia and mechanisms of resistance to BCR-ABL1 TKIs will benefit patients and also provide a blueprint for similar discovery in other cancers.
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影响因子：
50.3
作者：
Gregory MA;Phang TL;Neviani P;Alvarez-Calderon F;Eide CA;O'Hare T;Zaberezhnyy V;Williams RT;Druker BJ;Perrotti D;Degregori J
通讯作者：
Degregori J
影响因子：
15.9
作者：
Chen, Yaoyu;Peng, Cong;Li, Shaoguang
通讯作者：
Li, Shaoguang
影响因子：
20.3
作者：
Kantarjian, Hagop M.;Cortes, Jorge E.;Gambacorti-Passerini, Carlo
通讯作者：
Gambacorti-Passerini, Carlo
DOI：
10.1056/nejmoa1306494
发表时间：
2013-11-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cortes JE;Kim DW;Pinilla-Ibarz J;le Coutre P;Paquette R;Chuah C;Nicolini FE;Apperley JF;Khoury HJ;Talpaz M;DiPersio J;DeAngelo DJ;Abruzzese E;Rea D;Baccarani M;Müller MC;Gambacorti-Passerini C;Wong S;Lustgarten S;Rivera VM;Clackson T;Turner CD;Haluska FG;Guilhot F;Deininger MW;Hochhaus A;Hughes T;Goldman JM;Shah NP;Kantarjian H;PACE Investigators
通讯作者：
PACE Investigators
影响因子：
28.2
作者：
Asmussen J;Lasater EA;Tajon C;Oses-Prieto J;Jun YW;Taylor BS;Burlingame A;Craik CS;Shah NP
通讯作者：
Shah NP