Kurmasheva Raushan T, Houghton Peter J
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105-2794, United States.
Curr Opin Chem Biol. 2007 Aug;11(4):424-32. doi: 10.1016/j.cbpa.2007.05.037. Epub 2007 Jul 24.
Intensive use of cytotoxic agents in multimodality therapeutic regimens has resulted in almost 80% five-year disease-free survival and cure in the majority of childhood cancer patients. However, such success has come at the expense of severe acute or delayed toxicities and an increased occurrence of secondary cancers. With an increasing understanding of the genetic changes that underlie transformation in childhood cancer, rational approaches using agents that target these transforming events are being developed. Current and future strategies in developing tumor-selective therapy using inhibitors of signaling pathways dysregulated in leukemias (FLT3, NOTCH1) and solid/brain tumors (ErbB1-4, IGF-IR, PTCH1), and the challenges in developing less toxic, but equally effective treatments in pediatric oncology are presented.
在多模式治疗方案中大量使用细胞毒性药物，已使大多数儿童癌症患者实现了近80%的五年无病生存率并治愈。然而，这种成功是以严重的急性或迟发性毒性以及继发性癌症发生率增加为代价的。随着对儿童癌症转化基础的基因变化的认识不断加深，正在开发使用针对这些转化事件的药物的合理方法。本文介绍了利用白血病（FLT3、NOTCH1）和实体瘤/脑肿瘤（ErbB1 - 4、IGF - IR、PTCH1）中失调的信号通路抑制剂开发肿瘤选择性疗法的当前和未来策略，以及在儿科肿瘤学中开发毒性较小但同样有效的治疗方法所面临的挑战。
