Tumor Biology Research Program

项目概要：肿瘤生物学研究 西尔维斯特综合癌症中心（西尔维斯特）肿瘤生物学（TB）研究计划，建立了 2014年，调查员包括来自11个部门/学科的42名调查员， 致癌信号传导、应激反应、发育途径、免疫信号传导和炎症。领导 联合领导人Wael El-Rifai，医学博士，博士和Ashok Saluja，博士，结核病计划拥有目前的研究资金 直接同行评审资金1160万美元的投资组合，包括来自国家癌症研究所（NCI）的590万美元。 该计划促进并协作整合了计划和中心内的癌症研究工作， 广泛，同时催化高影响力的发现，以解决未满足的需求，西尔维斯特的四个县 集水区该计划的主要目标是了解癌症是如何发生和发展的， 癌细胞、肿瘤基质和免疫细胞之间的关键相互作用。结核病患者也利用这些知识 确定新的治疗方法，目标是基本的生物学和分子特征， 癌细胞为了实现这些目标，TB成员优先考虑了三个科学目标：1）阐明 肿瘤发生和发展的潜在机制; 2）确定炎症和免疫如何影响肿瘤的发生和发展。 影响肿瘤发生和肿瘤微环境; 3）研究生物学和分子基础 有针对性的治疗方法。来自西尔维斯特四个共享资源的专业知识和技术支持- 生物统计学和生物信息学，肿瘤基因组学，流式细胞术，以及基于行为和社区的 研究-支持结核病研究工作。自2014年以来，项目成员已经发表了337篇同行评审， 癌症相关论文：33%代表协作团队科学，21%是项目内论文（高于14%） 2014年），18%是跨计划（2014年为13%），66%涉及与外部合作 其中28%包括来自NCI指定癌症中心的科学家。近期结核病研究重点 包括发现氧化应激和抗氧化反应促进对雄激素的抵抗 去势抵抗性前列腺癌的剥夺疗法;可使用适体靶向siRNA方法 靶向T细胞并增强抗肿瘤免疫力; STING依赖性胞浆DNA传感介导先天性 免疫原性肿瘤的免疫识别; NACK是NOTCH转录激活的组成部分 一种可以靶向癌细胞的复合物;一种CK 1 α（SSTC 3）的小分子激活剂， 胃肠道毒性最小的WNT抑制剂; JAK/STAT 3和HSP 70重塑肿瘤微环境， 介导胰腺癌的治疗抗性。利用西尔维斯特的基础设施，结核病公司- 领导者与计划成员合作，促进科学发现，并制定新的举措， 利用新兴的科学思想和技术，促进合作，创新， 基础研究

PROJECT SUMMARY: TUMOR BIOLOGY RESEARCH PROGRAM The Sylvester Comprehensive Cancer Center (Sylvester) Tumor Biology (TB) Research Program, established in 2014, comprises 42 investigators representing 11 departments/disciplines with expertise spanning oncogenic signaling, stress response, developmental pathways, immune signaling, and inflammation. Led by Co-Leaders Wael El-Rifai, MD, PhD, and Ashok Saluja, PhD, the TB program holds a current research funding portfolio of $11.6M in direct peer-reviewed funding, including $5.9M from the National Cancer Institute (NCI). The program facilitates and collaboratively integrates cancer research efforts within the program and center- wide, while catalyzing high-impact discoveries to address the unmet needs of Sylvester’s four-county catchment area. The program’s primary goals are to understand how cancers arise and progress and to define key interactions between cancer cells, tumor stroma, and immune cells. TB members also use that knowledge to identify novel therapeutic approaches that target the fundamental biological and molecular features of cancer cells. To accomplish these goals, TB members have prioritized three scientific aims: 1) Elucidate mechanisms underlying tumor initiation and progression; 2) Determine how inflammation and immunity influence tumorigenesis and the tumor microenvironment; and 3) Investigate the biological and molecular basis of targeted therapeutic approaches. Expertise and technical support from Sylvester’s four shared resources— Biostatistics and Bioinformatics, Onco-Genomics, Flow Cytometry, and Behavioral and Community-Based Research—support TB research efforts. Since 2014, program members have published 337 peer-reviewed, cancer-relevant papers: 33% represent collaborative team science, 21% are intra-programmatic (up from 14% in 2014), 18% are inter-programmatic (up from 13% in 2014), 66% involve collaboration with external institutions, and 28% include scientist from NCI-designated cancer centers. Recent TB research highlights include the discoveries that oxidative stress and antioxidant response promote resistance to androgen deprivation therapy in castration-resistant prostate cancers; aptamer-targeted siRNA approaches can be used to target T cells and enhance anti-tumor immunity; STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors; NACK is an integral component of NOTCH transcription activation complex that can be targeted in cancer cells; a small molecular activator of CK1α (SSTC3) that acts as a novel WNT inhibitor with minimal GI toxicity; and JAK/STAT3 and HSP70 remodel tumor microenvironment and mediate therapeutic resistance in pancreatic cancer. Capitalizing on Sylvester’s infrastructure, the TB Co- Leaders work with program members to promote scientific discoveries and develop new initiatives that leverage emerging scientific ideas and technologies to foster collaborative, innovative, catchment area-relevant basic research.