Klinik für Hämatologie und Onkologie mit der Sektion Pneumologie, Onkologisches Zentrum, Universitäts-Klinikum Hamburg-Eppendorf, Hamburg, Germany.
Expert Rev Anticancer Ther. 2012 Sep;12(9):1121-7. doi: 10.1586/era.12.84.
The dual Src/Abl kinase inhibitor bosutinib (SKI-606) targets the tyrosine kinase brc-abl, the key enzyme in the development of chronic myeloid leukemia (CML). In clinical trials, bosutinib yielded promising results with regard to efficacy, tolerability and toxicity in first-, second- and third-line therapy of CML patients. Remarkably, bosutinib is able to overcome most imatinib-resistant BCR-ABL1-1 mutations except V299L and T315I. Mostly, low-to-moderate grade gastrointestinal toxicitis are the most common treatment-emergent adverse events observed under bosutinib. Unlike other tyrosine kinase inhibitors approved for CML treatment to date, bosutinib shows only minimal inhibitory activity against c-KIT and the PDGF receptor. This may be causative for its favorable hematologic toxicity profile. In this review, the authors give an overview on the mechanism of action and currently available preclinical and clinical data for bosutinib in CML.
双重Src/Abl 激酶抑制剂博舒替尼（SKI-606）针对酪氨酸激酶 brc-abl，这是慢性髓性白血病（CML）发展的关键酶。在临床试验中，博舒替尼在 CML 患者的一线、二线和三线治疗中显示出令人鼓舞的疗效、耐受性和毒性结果。值得注意的是，博舒替尼能够克服除 V299L 和 T315I 之外的大多数伊马替尼耐药 BCR-ABL1-1 突变。大多数情况下，低至中度胃肠道毒性是博舒替尼治疗下观察到的最常见的治疗后不良事件。与迄今为止批准用于 CML 治疗的其他酪氨酸激酶抑制剂不同，博舒替尼对 c-KIT 和 PDGF 受体仅表现出最小的抑制活性。这可能是其有利的血液学毒性特征的原因。在这篇综述中，作者概述了博舒替尼在 CML 中的作用机制和目前可用的临床前和临床数据。
