van der Sligte Naomi E, Kampen Kim R, de Bont Eveline S J M
Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700, Groningen, The Netherlands.
Cell Mol Life Sci. 2015 Oct;72(19):3589-98. doi: 10.1007/s00018-015-2019-7. Epub 2015 Aug 31.
The introduction of kinase inhibitors in cancer medicine has transformed chronic myeloid leukemia from a fatal disease into a leukemia subtype with a favorable prognosis by interfering with the constitutively active kinase BCR-ABL. This success story has resulted in the development of multiple kinase inhibitors. We are currently facing significant limitations in implementing these kinase inhibitors into the clinic for the treatment of pediatric malignancies. As many hallmarks of cancer are known to be regulated by intracellular protein signaling networks, we suggest focusing on these networks to improve the implementation of kinase inhibitors. This viewpoint will provide a short overview of currently used strategies for the implementation of kinase inhibitors as well as reasons why kinase inhibitors have unfortunately not yet been widely used for the treatment of pediatric cancers. We argue that by using a future personalized medicine strategy combining kinomics, proteomics, and drug screen approaches, the gap between pediatric cancers and the use of kinase inhibitors may be bridged.
激酶抑制剂在癌症医学中的引入,通过干扰持续激活的激酶BCR-ABL,已将慢性髓性白血病从一种致命疾病转变为预后良好的白血病亚型。这一成功案例推动了多种激酶抑制剂的研发。目前,我们在将这些激酶抑制剂应用于临床治疗小儿恶性肿瘤方面面临重大限制。由于已知许多癌症特征受细胞内蛋白质信号网络调控,我们建议聚焦于这些网络,以改善激酶抑制剂的应用。本文观点将简要概述目前使用的激酶抑制剂应用策略,以及激酶抑制剂尚未广泛用于治疗小儿癌症的原因。我们认为,通过采用结合激酶组学、蛋白质组学和药物筛选方法的未来个性化医学策略,或许可以弥合小儿癌症与激酶抑制剂应用之间的差距。