Druker Brian J
Leukemia Center, Oregon Health & Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
Trends Mol Med. 2002;8(4 Suppl):S14-8. doi: 10.1016/s1471-4914(02)02305-5.
STI571 (Gleevec, imatinib mesylate) exemplifies the successful development of a rationally designed, molecularly targeted therapy for the treatment of a specific cancer. This article reviews the identification of Bcr-Abl as a therapeutic target in chronic myelogenous leukemia and the steps in the development of an agent to inactivate this abnormality. Issues related to clinical trials of molecularly targeted agents are discussed, including dose and patient selection and possible mechanisms of resistance to STI571. Finally, the potential use of STI571 with different tumors and the translation of this paradigm to other malignancies are explored.
STI571（格列卫，甲磺酸伊马替尼）是成功研发出的一种针对特定癌症的合理设计的分子靶向治疗药物的典范。本文回顾了将Bcr-Abl确定为慢性粒细胞白血病治疗靶点的过程，以及开发一种使该异常失活的药物的各个步骤。讨论了与分子靶向药物临床试验相关的问题，包括剂量、患者选择以及对STI571耐药的可能机制。最后，探讨了STI571在不同肿瘤中的潜在应用以及这种模式向其他恶性肿瘤的转化。
