Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
Terry Fox Laboratory, British Columbia Cancer Agency and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Drug Discov Today. 2019 Jul;24(7):1355-1369. doi: 10.1016/j.drudis.2019.05.007. Epub 2019 May 15.
Chronic myeloid leukemia cells are armed with several resistance mechanisms that can make current drugs ineffective. A better understanding of resistance mechanisms is yielding new approaches to management of the disease. Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm the hallmark of which, the breakpoint cluster region-Abelson (BCR-ABL) oncogene, has been the target of tyrosine kinase inhibitors (TKIs), which have significantly improved the survival of patients with CML. However, because of an increase in TKI resistance, it is becoming imperative to identify resistance mechanisms so that drug therapies can be better prescribed and new agents developed. In this review, we discuss the various BCR-ABL-dependent and -independent mechanisms of resistance observed in CML, and the range of therapeutic solutions available to overcome such resistance and to ultimately improve the survival of patients with CML.
慢性髓性白血病细胞拥有多种耐药机制，这些机制会使目前的药物无效。对耐药机制的更好理解产生了治疗该疾病的新方法。慢性髓性白血病（CML）是一种骨髓增生性肿瘤，其标志是断裂点簇区-Abelson（BCR-ABL）致癌基因，该基因一直是酪氨酸激酶抑制剂（TKI）的靶点，这显著改善了 CML 患者的生存率。然而，由于 TKI 耐药性的增加，确定耐药机制变得至关重要，以便更好地开具药物治疗方案并开发新的药物。在这篇综述中，我们讨论了 CML 中观察到的各种 BCR-ABL 依赖性和非依赖性耐药机制，以及克服这种耐药性并最终改善 CML 患者生存的各种治疗方法。
