Precision Cancer Medicine and Investigational Therapeutics

摘要-实体肿瘤治疗计划 杜克癌症研究所的实体肿瘤治疗计划(STT)专注于针对疾病的药物 以下疾病组的发展和检测：胃肠癌(食道癌、胃癌、小细胞癌 肠、结直肠、肛门、肝胆和胰腺癌)、泌尿生殖道癌(肾、膀胱、前列腺癌、 癌症包括睾丸癌、胸癌(肺癌)、肉瘤、黑色素瘤和头颈癌。大多数实体肿瘤共享 调节发育和动态平衡的主要信号通路的共同变化，包括 表皮生长因子、转化生长因子-β、血小板衍生生长因子、血管内皮生长因子、成纤维细胞生长因子受体、胰岛素样生长因子、HH、Wnt、Src和c-Met途径。此外，实体肿瘤还会分享 对肿瘤微环境(即免疫系统、血管生成)的保守作用。此外，获得洞察力 进入癌细胞自主和肿瘤微环境的改变，这将导致 临床实践需要开发更多相关的临床前模型来执行联合临床试验。 因此，该计划的首要目标是增加针对疾病的药物开发和测试 杜克大学基于早期药物发现和领导开发努力的研究人员发起的试验 大学。STT的主题是统一这些疾病地点的研究努力，以提高疾病的特异性 研究人员启动了临床试验。STT被组织成三个焦点组：信号转导通路， 肿瘤微环境/免疫治疗和临床前模型。这些努力将使我们能够利用 杜克大学早期药物发现和领导开发工作，增加针对疾病的药物 研究人员发起的试验的开发和测试，包括第一阶段实验疗法。 与癌症控制和人口科学项目和卫生公平办公室密切合作 还支持对包括成本在内的癌症医疗保健措施进行种族分层临床试验和评估 和健康经济学，以及结果，包括患者报告的结果、质量和基于价值的护理，以及 癌症差异。NCI将提供翻译和临床试验开发的机会 实验治疗学临床试验网络I期重点(ET-CTN)拨款和国家 临床试验网络(NCTN)领导学术站点资助，这两个项目都由本项目的研究人员领导。 STT由来自3个不同部门的12个不同部门的60名初级成员和26名二级成员组成 杜克大学内的学校。为主要计划成员提供的总资金为2000万美元，其中440万美元为同业 经过审查，其中包括来自NCI的180万美元。2014-2018年间，计划成员在Peer- 在审查的期刊中，33%是方案内的，39%是方案间的合作。在.期间 目前的赠款期间，该计划招募了3823名受试者参加所有试验，2216名受试者参加干预性试验，1516名受试者参加 治疗试验。

ABSTRACT – SOLID TUMOR THERAPEUTICS PROGRAM The Duke Cancer Institute’s Solid Tumor Therapeutics Program (STT) focuses on disease-specific drug development and testing in the following disease groups: gastrointestinal cancers (esophageal, gastric, small intestine, colorectal, anal, hepatobiliary and pancreatic), genitourinary cancers (kidney, bladder, prostate, testicular), thoracic cancers (lung), sarcoma, melanoma and head and neck cancers. Most solid tumors share common alterations in the major signaling pathways regulating development and homeostasis, including the EGF, TGF-β, PDGF, VEGF, FGFR, IGF, Hh, Wnt, Src and c-Met pathways. In addition, solid tumors share conserved roles for the tumor microenvironment (i.e., immune system, angiogenesis). Further, gaining insight into the cancer cell autonomous and tumor microenvironment alterations that will result in improvements in clinical practice requires the development of more relevant pre-clinical models to execute co-clinical trials. Accordingly, the Program’s overarching goal is to increase disease-specific drug development and testing with investigator-initiated trials based on the early stage drug discovery and lead development efforts at Duke University. The STT theme is to align the research efforts across these disease sites to increase disease-specific investigator initiated clinical trials. STT is organized into three focus groups: Signal Transduction Pathways, Tumor Microenvironment/Immunotherapy, and Preclinical Modeling. These efforts will enable us to leverage early stage drug discovery and lead development efforts at Duke, and increase disease-specific drug development and testing with investigator-initiated trials, including Phase I experimental therapeutics. Close collaboration with the Cancer Control and Population Sciences Program and Office of Health Equity also enables race-stratified clinical trials and assessing of cancer healthcare delivery measures including cost and health economics, and outcomes including patient-reported outcomes, quality and value-base care, and cancer disparities. Opportunities for translational and clinical trial development will occur through the NCI Experimental Therapeutics Clinical Trials Network with Phase I emphasis (ET-CTN) grant and the National Clinical Trials Network (NCTN) lead academic site grant, both of which are led by investigators in this Program. STT is comprised of 60 primary members and 26 secondary members from 12 different departments in 3 schools within Duke University. Total funding for primary program members is $20M, of which $4.4M is peer reviewed, including $1.8M from the NCI. From 2014-2018, Program members published 1,395 papers in peer- reviewed journals, 33% were intra-programmatic and 39% were inter-programmatic collaborations. During the current grant period, the Program enrolled 3,823 subjects to all trials, 2,216 to interventional trials, and 1,516 to treatment trials.