05 Brain Cancer

项目摘要/摘要 脑癌计划(BCP)是一个多学科的基础、翻译和临床研究计划，包括 86名成员(36名主要成员和50名助理成员)。领导力由内科科学家提供：艾米·海姆伯格 和弗雷德里克·朗，两人都是神经外科医生；胡安·富尤-玛格丽托，实验室研究员；以及约翰 德·格鲁特，神经肿瘤学家。BCP的总体目标是确定遗传和分子决定因素 研究原发和转移性脑肿瘤的形成和发展，并利用这些知识来改善 通过有针对性的生物和小分子治疗，提高患者的存活率和生活质量。这个 该计划有三个具体目标。目标1：开发有效的病毒和免疫治疗策略 利用胶质母细胞瘤的异质性。目标2：确定如何优化中心的目标方法 神经系统肿瘤。目标3：确定促进中枢神经系统发育的因素 转移，制定防止其形成的策略，及早发现或识别高危患者，以及 确定最佳治疗方法的优先顺序。BCP的年度直接同行审查资金为570万美元，其中包括 脑癌孢子。在同行评审的资金总额中，210万美元(37%)来自NCI赠款，360万美元来自 其他同行评议的资料来源。BCP成员在同行评议的期刊上发表了703篇文章 过去6年，其中362年(51%)为方案内，170年(24%)为方案间，485年(69%) 涉及外部合作。41%的出版物与IF&>5一起出现在期刊上，以及 13%的人出现在IF&GT；10的期刊上，包括《自然》、《癌细胞》、《摩尔细胞》、《柳叶刀》、《临床杂志》、 J Natl癌症研究所、J Clin Invest和Nat Genet。成就包括对癌症的重大贡献 基因组图谱及其在国际胶质母细胞瘤适应性全球创新学习中的关键领导作用 环境贝叶斯临床试验。在上一次赠款期间，BCP成员提出了重要的 在评价胶质母细胞瘤干细胞转录组可塑性和抗辐射能力方面的贡献 (Bhat等人，癌细胞，2013)以及颤动在自我更新和防止终末分化中的作用 (胡静等人，Proc Natl Acad Sci USA，2013；Shingu等人，NAT Genet，2017)，Wnt5A in Driving GSC 分化为支持侵袭性胶质母细胞瘤细胞的内皮样细胞(Hu B et al，Cell，2016)，以及 PKM2在肿瘤生物学和转移计划中改变细胞代谢和细胞周期进展的作用 (Yang et al，Mol Cell，2012；Yang et al，Cell，2012；酱Y et al，Mol Cell，2014；酱Y et al，NAT Commun， 2014年)。BCP成员的另一个重要进展是脑转移瘤后立体定向放射外科的使用 切除作为全脑放射治疗的替代方案，影响了这些患者的护理标准 全国患者(Mahajan A等人，《柳叶刀》，2017年)。我们已经看到Whole的使用量减少了50%- 德克萨斯大学MD安德森癌症中心的脑部照射。

PROJECT SUMMARY/ABSTRACT The Brain Cancer Program (BCP), a multidisciplinary basic, translational, and clinical research program, includes 86 members (36 primary and 50 associate). Leadership is provided by physician-scientists: Amy Heimberger and Frederick Lang, both neurosurgeons; Juan Fueyo-Margareto, a laboratory-based investigator; and John de Groot, a neuro-oncologist. The overall goal of the BCP is to identify the genetic and molecular determinants of primary and metastatic brain tumor formation and progression and to use this knowledge to improve the survival and quality of life of patients through specifically targeted biological and small-molecule therapies. The program has 3 specific aims. Aim 1: To develop effective viral and immunotherapeutic treatment strategies that exploit glioblastoma heterogeneity. Aim 2: To determine how to optimize targeted approaches for central nervous system tumors. Aim 3: To define factors that promote the development of central nervous system metastases, devise strategies to prevent their formation, develop early detection or identify at-risk patients, and prioritize optimal therapeutic approaches. The BCP's annual direct peer-reviewed funding is $5.7M, including a Brain Cancer SPORE. Of the total peer-reviewed funding, $2.1M (37%) is from NCI grants, and $3.6M is from other peer-reviewed sources. BCP members have authored 703 publications in peer-reviewed journals over the past 6 years, of which 362 (51%) were intra-programmatic, 170 (24%) were inter-programmatic, and 485 (69%) involved external collaborations. Forty-one percent of publications have appeared in journals with IF >5, and 13% have appeared in journals with IF >10, including Nature, Cancer Cell, Mol Cell, Lancet Oncol, J Clin Oncol, J Natl Cancer Inst, J Clin Invest, and Nat Genet. Accomplishments include major contributions to The Cancer Genome Atlas and key leadership roles in the international glioblastoma Adaptive Global Innovative Learning Environment Bayesian Clinical Trial. During the last grant period, members of the BCP made important contributions in evaluating transcriptome plasticity and radiation resistance in glioblastoma stem cells (GSCs) (Bhat et al, Cancer Cell, 2013) and the roles of Quaking in self-renewal and preventing terminal differentiation of GSCs (Hu J et al, Proc Natl Acad Sci USA, 2013; Shingu et al, Nat Genet, 2017), WNT5a in driving GSC differentiation into endothelial-like cells that support invasive glioblastoma cells (Hu B et al, Cell, 2016), and PKM2 in altering cell metabolism and cell-cycle progression with the Cancer Biology and Metastasis Program (Yang et al, Mol Cell, 2012; Yang et al, Cell, 2012; Jiang Y et al, Mol Cell, 2014; Jiang Y et al, Nat Commun, 2014). Another important advance by BCP members is the use of stereotactic radiosurgery after brain metastasis resection as an alternative to whole-brain radiotherapy, which has influenced the standard of care for these patients nationally (Mahajan A et al, Lancet Oncol, 2017). We have seen a 50% decrease in the use of whole- brain irradiation at The University of Texas MD Anderson Cancer Center.