Precision Cancer Medicine and Investigational Therapeutics

摘要-实体肿瘤治疗 杜克癌症研究所的实体肿瘤治疗项目（STT）专注于疾病特异性药物 在以下疾病组中的开发和测试：胃肠道癌（食道癌、胃癌、小胃癌、胃癌和胃癌） 肠、结肠直肠、肛门、肝胆和胰腺），泌尿生殖系统癌症（肾，膀胱，前列腺， 睾丸癌）、胸癌（肺癌）、肉瘤、黑色素瘤和头颈癌。大多数实体瘤 调节发育和体内平衡的主要信号通路的常见改变，包括 EGF、TGF-β、PDGF、VEGF、FGFR、IGF、Hh、Wnt、Src和c-Met途径。此外，实体瘤占 肿瘤微环境的保守作用（即，免疫系统、血管生成）。此外，获得洞察力 进入癌细胞自主和肿瘤微环境的改变，这将导致改善， 临床实践需要开发更相关的临床前模型以执行共同临床试验。 因此，该计划的总体目标是增加针对特定疾病的药物开发和测试 在杜克的早期药物发现和先导开发工作的基础上， 大学STT的主题是协调这些疾病部位的研究工作，以增加疾病特异性 研究者发起的临床试验。STT分为三个焦点小组：信号转导通路， 肿瘤微环境/免疫治疗和临床前建模。这些努力将使我们能够利用 早期药物发现和领导杜克的开发工作，并增加疾病特异性药物 开发和测试与兴奋剂启动的试验，包括I期实验疗法。 与癌症控制和人口科学计划以及健康公平办公室密切合作 还可以进行种族分层的临床试验，并评估癌症医疗保健提供措施，包括成本 和卫生经济学，以及包括患者报告结局、质量和基于价值的护理在内的结局，以及 癌症差异转化和临床试验开发的机会将通过NCI出现 实验治疗药物临床试验网络与I期重点（ET-CTN）赠款和国家 临床试验网络（NCTN）领导学术研究中心赠款，这两个都是由本计划的研究者领导的。 短期培训小组由来自三个不同部门的60名主要成员和26名次要成员组成， 杜克大学的所有学校。主要计划成员的总资金为2000万美元，其中440万美元是同行 审查，包括来自NCI的180万美元。从2014年到2018年，项目成员在同行中发表了1，395篇论文， 评审期刊中，33%是项目内合作，39%是项目间合作。期间 在当前的资助期内，该计划招募了3，823名受试者参加所有试验，2，216名参与干预性试验，1，516名参与干预性试验。 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.