05 Brain Cancer

项目总结/摘要 脑癌计划（BCP）是一个多学科的基础，转化和临床研究计划，包括 86名成员（36名主要成员和50名副成员）。领导是由医生科学家提供：艾米海姆伯格 和弗雷德里克·朗，都是神经外科医生;胡安·富约-托托，一名实验室调查员;约翰· 神经肿瘤学家德·格鲁特BCP的总体目标是确定遗传和分子决定因素 原发性和转移性脑肿瘤的形成和进展，并利用这些知识来改善 通过特异性靶向生物和小分子治疗，提高患者的生存率和生活质量。的 方案有三个具体目标。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：确定如何优化针对中央 神经系统肿瘤目的3：确定促进中枢神经系统发育的因素 转移，制定策略以防止其形成，开发早期检测或识别风险患者，以及 优先考虑最佳治疗方法。BCP的年度直接同行评审资金为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 其他同行评审来源。BCP成员在2010年在同行评审期刊上发表了703篇论文。 过去6年，其中362（51%）是计划内的，170（24%）是计划间的，485（69%） 涉及外部合作。41%的出版物出现在IF >5的期刊上， 13%发表在IF >10的期刊上，包括Nature，Cancer Cell，Mol Cell，Lancet Oncol，J Clin Oncol， J Natl Cancer Inst、J Clin Invest和Nat Genet.成就包括对癌症的重大贡献 基因组图谱和国际胶质母细胞瘤适应性全球创新学习的关键领导角色 环境贝叶斯临床试验。在上一个赠款期间，BCP的成员 在评价胶质母细胞瘤干细胞（GSC）的转录组可塑性和辐射抗性方面的贡献 (Bhat等人，Cancer Cell，2013）和Quaking在自我更新和防止终末分化中的作用。 （Hu J et al，Proc Natl Acad Sci USA，2013;神宫et al，Nat Genet，2017），WNT 5a在驱动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），和 PKM 2在改变细胞代谢和细胞周期进程中的作用 (Yang等人，Mol Cell，2012; Yang等人，Cell，2012; Jiang Y等人，Mol Cell，2014; Jiang Y等人，Nat Commun， 2014）。BCP成员的另一个重要进展是脑转移后立体定向放射外科的使用 切除作为全脑放疗的替代方案，这影响了这些患者的护理标准。 全国范围内的患者（Mahajan A et al，Lancet Oncol，2017）。我们已经看到了50%的减少，在使用整个- 得克萨斯大学医学博士安德森癌症中心的脑辐射。

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.