Department of Hematologic Malignancies, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Hematol Oncol Clin North Am. 2010 Apr;24(2):423-41. doi: 10.1016/j.hoc.2010.02.010.
Preliminary therapeutic successes have prompted a new wave of clinical trials enrolling patients with myelodysplastic syndromes (MDS), using compounds with a broad range of potential mechanisms of action. This article discusses several of the agents currently in development for MDS, reviewing clinical trial data related to five classes of novel therapeutics: clofarabine, a halogenated purine nucleoside analog; ezatiostat (TLK199), a glutathione analog that indirectly activates c-Jun kinase; tipifarnib, a farnesyltransferase inhibitor; laromustine (cloretazine), an alkylating agent with a metabolite that inhibits one mechanism of DNA damage repair; and eight drugs that inhibit histone deacetylase. Although MDS are still difficult clinical problems, and most patients with MDS still succumb to disease-related complications within 3 to 5 years of diagnosis, ongoing development of novel agents promises that there will be new treatment options for patients within the next 5 to 10 years.
初步的治疗成功促使了一波新的临床试验，招募了骨髓增生异常综合征（MDS）患者，使用具有广泛潜在作用机制的化合物。本文讨论了目前正在开发的几种用于 MDS 的药物，回顾了与五类新型治疗药物相关的临床试验数据：氯法拉滨，一种卤化嘌呤核苷类似物；ezatiostat（TLK199），一种间接激活 c-Jun 激酶的谷胱甘肽类似物；tipifarnib，一种法尼酰基转移酶抑制剂；laromustine（cloretazine），一种烷化剂，其代谢物可抑制一种 DNA 损伤修复机制；以及八种抑制组蛋白去乙酰化酶的药物。尽管 MDS 仍然是临床难题，而且大多数 MDS 患者在诊断后 3 至 5 年内仍因疾病相关并发症而死亡，但新型药物的不断开发有望在未来 5 至 10 年内为患者提供新的治疗选择。
