Characterization of Xenograft Models of Childhood Cancers

该阵列项目是与儿童肿瘤小组（COG）第一阶段联盟和癌症治疗评估项目（CTEP）合作进行的，部分外部资金由NCI提供。这与《儿童最佳药物法案》中体现的一些要求是一致的，该法案规定，国家癌症研究所所长应扩大、加强和协调该研究所在临床前模型开发方面的研究活动，以评估哪些治疗方法可能对治疗儿童癌症有效。这个项目有四个主要目标。(1)通过cDNA微阵列确定目前使用的儿童癌症模型（异种移植物）中哪一种与起源癌症最接近。(2)开发该临床前面板的组织和细胞微阵列以及蛋白裂解物阵列，以确定癌症相关的分子靶点和信号通路，这些靶点和信号通路可能被用于治疗，以改善患有癌症的儿童的预后。(3)将这些组织和蛋白质阵列作为试剂提供给壁外和壁内研究社区的合格研究人员。(4)鉴定含有与人类癌症中发现的相同的可药物突变的异种移植物。该项目将通过确定与原发癌症最相似的最佳异种移植模型来促进儿童癌症药物的开发，并将成为识别分子靶点和细胞信号谱的资源，并将用于后续测试新的抗癌药物对儿童癌症的潜在活性。这一资源有可能加快发现儿童癌症新治疗靶点的步伐，并促进对儿童癌症有活性的新分子靶向药物的临床应用，靶点如在这些癌症中独特表达的死亡途径基因。

This array project is being conducted in collaboration with the Children's Oncology Group (COG) Phase 1 Consortium and the Cancer Therapy Evaluation Program (CTEP) and was partially externally funded by a grant from the NCI. It is in accord with some of the requirement embodied in the Best Pharmaceuticals for Children Act which stated that the Director of the National Cancer Institute shall expand, intensify, and coordinate the activities of the Institute with respect to research on the development of preclinical models to evaluate which therapies are likely to be effective for treating pediatric cancer. There are four main objectives of this project. (1) To determine which of the currently utized pediatric cancer models (xenograft) most closely resembles the cancer(s) of origin by cDNA microarrays. (2) To develop tissue and cell microarrays and protein lysate arrays of this preclinical panel, for the purpose of identifying cancer-related molecular targets and signaling pathways that may be therapeutically exploited to improve the outcome for children that suffer from cancer. (3) To provide these tissue and protein arrays as reagents to qualified investigators in the extra- and intra-mural research community. (4) Identify xenografts that contain the same druggable mutations as those found in the human cancer. This project will facilitate pediatric cancer drug development by identifying the best xenograft models that are the most similar to the cancer of origin, and will be a resource to use in identifying molecular targets and cell signal profiles, and for subsequent testing new anti-cancer agents for their potential activity against childhood cancers. This resource has the potential to increase the pace of new therapeutic target discovery for childhood cancers and to facilitate the clinical use of new molecularly targeted agents active against childhood cancera, targets such as death pathway genes, uniquely expressed in these cancers.