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Targeted CML therapy: controlling drug resistance, seeking cure

机译:有针对性的CML治疗:控制耐药性,寻求治愈

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Targeted cancer therapy with imatinib (Gleevec) has the capability to drive chronic myeloid leukemia (CML) into clinical remission. Some patients, particularly those with advanced disease, develop resistance to imatinib. To counteract this problem, two new BCR-ABL kinase inhibitors for imatinib-refractory disease are currently in clinical trials: the imatinib derivative AMN107 and the dual-specificity SRC/ABL inhibitor dasatinib. Using imatinib to reduce leukemic burden also facilitates the detailed investigation into how the persistence of CML disease depends on BCR-ABL signaling, particularly within the leukemic stem cell compartment. Mathematical models of drug resistance and disease relapse, in addition to experimental systems that recapitulate crucial aspects of advanced disease have deepened our understanding of CML biology. Together, these advances are contributing to a high level of disease control, and might ultimately lead to disease eradication.
机译:伊马替尼(Gleevec)的靶向癌症治疗具有将慢性粒细胞白血病(CML)驱使到临床缓解的能力。一些患者,尤其是那些患有晚期疾病的患者,对伊马替尼产生抗药性。为了解决这个问题,目前正在临床试验中使用两种新的伊马替尼难治性疾病的BCR-ABL激酶抑制剂:伊马替尼衍生物AMN107和双特异性SRC / ABL抑制剂达沙替尼。使用伊马替尼减轻白血病负担也有助于详细研究CML疾病的持久性如何依赖BCR-ABL信号传导,特别是在白血病干细胞腔室内。耐药性和疾病复发的数学模型,以及概括晚期疾病关键方面的实验系统,加深了我们对CML生物学的理解。这些进步共同促进了高水平的疾病控制,并最终可能导致疾病的根除。

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