University of Turin, Department of Clinical and Biological Sciences, S. Luigi Hospital, Regione Gonzole 10, 10043, Orbassano Turin, Italy.
Expert Opin Emerg Drugs. 2010 Jun;15(2):175-84. doi: 10.1517/14728211003621220.
The deregulated tyrosine kinase activity of BCR-ABL has been demonstrated to be necessary and sufficient to maintain leukemia phenotype of chronic myeloid leukemia (CML) which, therefore, represents a unique model for the development of molecular targeted therapy and the first disease in which the tyrosine kinase inhibitors (TKIs) completely changed the therapeutical approach. The impressive results of TKIs in this model have been overshadowed by the development of clinical resistance.
This review focuses on clinical results with imatinib therapy and second generation TKIs. Furthermore, a summary of the guidelines for the management of TKI resistant patients is provided together with a description of the new drugs in clinical or preclinical phases which are developing to overcome resistance.
Future perspective for the 'cure' of CML patients and new drugs designed for this purpose are suggested.
CML therapy has dramatically changed in the last few years due to the introduction of targeted therapy. Studies on new drugs targeting different pathways other than BCR-ABL are ongoing to improve the clinical results.
已证明 BCR-ABL 的酪氨酸激酶活性失调对于维持慢性髓细胞白血病 (CML) 的白血病表型是必要且充分的，因此，它代表了分子靶向治疗发展的独特模型，也是首个完全改变治疗方法的酪氨酸激酶抑制剂 (TKI) 的疾病。在这种模型中，TKI 的令人印象深刻的结果因临床耐药性的发展而黯然失色。
本文重点介绍了伊马替尼治疗和第二代 TKI 的临床结果。此外，还提供了 TKI 耐药患者管理指南的摘要，以及描述了正在临床或临床前阶段开发以克服耐药性的新药。
为 CML 患者的“治愈”和为此目的设计的新药提供了未来展望。
由于靶向治疗的引入，CML 治疗在过去几年发生了巨大变化。正在进行针对 BCR-ABL 以外的不同途径的新药研究，以改善临床结果。
