Diehl Kathleen M, Keller Evan T, Ignatoski Kathleen M Woods
Department of Urology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0940, USA.
Mol Cancer Ther. 2007 Feb;6(2):418-27. doi: 10.1158/1535-7163.MCT-06-0603.
Although oncogenes and their transformation mechanisms have been known for 30 years, we are just now using our understanding of protein function to abrogate the activity of these genes to block cancer growth. The advent of specific small-molecule inhibitors has been a tremendous step in the fight against cancer and their main targets are the cellular counterparts of viral oncogenes. The best-known example of a molecular therapeutic is Gleevec (imatinib). In the early 1990s, IFN-alpha treatment produced a sustained cytologic response in approximately 33% of chronic myelogenous leukemia patients. Today, with Gleevec targeting the kinase activity of the proto-oncogene abl, the hematologic response rate in chronic myelogenous leukemia patients is 95% with 89% progression-free survival at 18 months. There are still drawbacks to the new therapies, such as drug resistance after a period of treatment, but the drawbacks are being studied experimentally. New drugs and combination therapies are being designed that will bypass the resistance mechanisms.
尽管癌基因及其转化机制已被知晓30年了，但我们直到现在才利用对蛋白质功能的理解来消除这些基因的活性，以阻止癌症生长。特异性小分子抑制剂的出现是抗癌斗争中的巨大进步，其主要靶点是病毒癌基因在细胞中的对应物。分子疗法最著名的例子是格列卫（伊马替尼）。20世纪90年代初，α干扰素治疗使约33%的慢性髓性白血病患者产生了持续的细胞学反应。如今，格列卫靶向原癌基因abl的激酶活性，慢性髓性白血病患者的血液学反应率为95%，18个月时无进展生存率为89%。新疗法仍有缺点，比如治疗一段时间后会产生耐药性，但这些缺点正在进行实验研究。正在设计能绕过耐药机制的新药和联合疗法。
