Weisberg Ellen, Griffin James D
Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Drug Resist Updat. 2003 Oct;6(5):231-8. doi: 10.1016/s1368-7646(03)00062-1.
Imatinib mesylate, an orally administered 2-phenylaminopyrimidine derivative that inhibits BCR/ABL tyrosine kinase activity, has shown great promise in the treatment of chronic myelogenous leukemia (CML). This small molecule, tyrosine kinase inhibitor, has also been shown to be effective against metastatic gastrointestinal stromal tumors (GISTs) expressing the stem cell factor (SCF) receptor kit. However, the threat of resistance in patients has prompted investigators to uncover the mechanisms whereby malignant cells develop resistance to imatinib, and has also led to the establishment of strategies designed to over-ride imatinib resistance. Here, we provide a comprehensive overview of the effectiveness of imatinib in the treatment of chronic, accelerated and blast crisis-phase CML, Philadelphia chromosome-positive (Ph+) acute lymphoid leukemia (ALL) and metastatic GIST. Established mechanisms of resistance to imatinib are discussed, as are novel therapeutic approaches to improving drug responsiveness by reversing development of imatinib resistance in patients.
甲磺酸伊马替尼是一种口服的2-苯基氨基嘧啶衍生物，可抑制BCR/ABL酪氨酸激酶活性，在慢性粒细胞白血病（CML）的治疗中显示出巨大前景。这种小分子酪氨酸激酶抑制剂也已被证明对表达干细胞因子（SCF）受体c-Kit的转移性胃肠道间质瘤（GIST）有效。然而，患者出现耐药性的威胁促使研究人员去揭示恶性细胞对伊马替尼产生耐药性的机制，也促使人们制定克服伊马替尼耐药性的策略。在此，我们全面概述了伊马替尼在治疗慢性、加速期和急变期CML、费城染色体阳性（Ph+）急性淋巴细胞白血病（ALL）和转移性GIST方面的有效性。讨论了已确定的伊马替尼耐药机制，以及通过逆转患者伊马替尼耐药性发展来提高药物反应性的新治疗方法。
