Dyer M A
St Jude Children's Research, Department of Developmental Neurobiology, Memphis, TN 38105, USA.
J Clin Pathol. 2004 Jun;57(6):561-76. doi: 10.1136/jcp.2003.009910.
Targeted cancer treatments rely on understanding signalling cascades, genetic changes, and compensatory programmes activated during tumorigenesis. Increasingly, pathologists are required to interpret molecular profiles of tumour specimens to target new treatments. This is challenging because cancer is a heterogeneous disease-tumours change over time in individual patients and genetic lesions leading from preneoplasia to malignancy can differ substantially between patients. For childhood tumours of the nervous system, the challenge is even greater, because tumours arise from progenitor cells in a developmental context different from that of the adult, and the cells of origin, neural progenitor cells, show considerable temporal and spatial heterogeneity during development. Thus, the underlying mechanisms regulating normal development of the nervous system also need to be understood. Many important advances have come from model mouse genetic systems. This review will describe several mouse models of childhood tumours of the nervous system, emphasising how understanding the normal developmental processes, combined with mouse models of cancer and the molecular pathology of the human diseases, can provide the information needed to treat cancer more effectively.
靶向癌症治疗依赖于对肿瘤发生过程中激活的信号级联、基因变化和补偿程序的理解。越来越多的病理学家需要解读肿瘤标本的分子特征，以确定新的治疗靶点。这具有挑战性，因为癌症是一种异质性疾病——肿瘤在个体患者中会随时间变化，并且从癌前病变发展到恶性肿瘤的基因损伤在不同患者之间可能有很大差异。对于儿童神经系统肿瘤，挑战更大，因为肿瘤起源于与成人不同的发育背景中的祖细胞，而且起源细胞，即神经祖细胞，在发育过程中表现出相当大的时间和空间异质性。因此，还需要了解调节神经系统正常发育的潜在机制。许多重要进展来自小鼠模型遗传系统。本综述将描述几种儿童神经系统肿瘤的小鼠模型，强调了解正常发育过程，结合癌症小鼠模型和人类疾病的分子病理学，如何能够提供更有效治疗癌症所需的信息。
