Tumor Biology Research Program

项目概要：肿瘤生物学研究计划 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 2014年，由代表11个部门/学科的42名调查员组成，他们的专业知识横跨 致癌信号、应激反应、发育途径、免疫信号和炎症。领头羊 共同领导Wael El-Rifai，医学博士和Ashok Saluja博士，结核病计划持有目前的研究资金 投资组合中有1160万美元的直接同行评审资金，其中包括来自国家癌症研究所(NCI)的590万美元。 该计划促进并协作地将癌症研究工作整合到该计划和中心- 广泛，同时催化高影响力的发现，以解决西尔维斯特的四个县未得到满足的需求 集水区。该计划的主要目标是了解癌症是如何产生和发展的，并确定 癌细胞、肿瘤间质和免疫细胞之间的关键相互作用。结核病成员也利用这一知识 找出新的治疗方法，以基本的生物学和分子特征为目标 癌细胞。为了实现这些目标，结核病成员优先考虑了三个科学目标：1)阐明 肿瘤发生和发展的机制；2)决定炎症和免疫 对肿瘤发生和肿瘤微环境的影响；3)研究其生物学和分子基础 有针对性的治疗方法。来自西尔维斯特的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、行为和社区 研究--支持结核病研究工作。自2014年以来，项目成员发表了337篇同行评议文章， 癌症相关论文：33%代表团队合作科学，21%代表计划内研究(高于14% 2014年)，18%是跨计划的(2014年为13%)，66%涉及与外部的协作 机构，28%包括来自NCI指定癌症中心的科学家。最近结核病研究的亮点 包括氧化应激和抗氧化反应促进雄激素抵抗的发现 耐去势前列腺癌的剥夺治疗；适体靶向siRNA方法可以使用 靶向T细胞，增强抗肿瘤免疫；刺样依赖胞浆DNA传感介导先天免疫 免疫原性肿瘤的免疫识别；NACK是Notch转录激活的重要组成部分 可靶向于癌细胞的复合体；一种CK1α的小分子激活剂(SSTC3)，作为一种新的 胃肠道毒性最小的WNT抑制剂；JAK/STAT3和HSP70重塑肿瘤微环境和 介导胰腺癌的治疗耐药。利用西尔维斯特的基础设施，TB Co- 领导人与计划成员合作，促进科学发现并开发新的倡议，以 利用新兴的科学思想和技术促进协作、创新、与流域相关 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.