Research Program - Experimental Therapeutics

摘要 实验治疗计划（ET）的总体使命是通过以下方式减轻癌症负担： 临床前和早期临床药物开发;确定最佳治疗组合和顺序; 确定活性药物疗效和耐药性的预后、预测和替代标志物， 通过战略合作，将我们的做法推广到我们的集水区和全国。ET包括组合 临床前、转化和临床研究，与其他项目（乳腺癌[BC]， 癌症预防和控制[CPC]和分子肿瘤学[MO]）。鉴于其临床重点，ET已经在 与最近的趋势和发现一致，这些趋势和发现对临床产生了影响，例如免疫疗法和 精准医疗目标1专注于靶向已知的癌症驱动途径。目标2的重点是 靶向肿瘤微环境（TME）和免疫系统。目标3的重点是开发药物， 用于癌症诊断、预后和治疗的生物标志物。重要成就包括完成一项 证明派姆单抗在胸腺癌中的疗效正在改变的药物启动试验（IIT） 治疗范例和工作证明了免疫抵抗的分子决定因素， 为免疫治疗寻找新的靶点ET由Giuseppe Giaccone，MD，PhD，前首席执行官领导。 美国国家癌症研究所（NCI）肿瘤学分支和肺癌和实验领域的领先专家 Anton Wellstein，MD，PhD，药理学家，其转化研究主要集中在肿瘤治疗上 间质相互作用和癌症进展至转移的机制。LCCC联盟由 乔治敦综合癌症中心，总部设在华盛顿，DC（LCCC-DC）和约翰·特雷尔 Hackensack Meridian Health癌症中心，位于新泽西州Hackensack（LCCC-NJ）。因此，LCCC 集水区由LCCC-DC和LCCC-NJ集水区定义。ET有43名成员，包括 来自Lombardi综合癌症中心六个部门的翻译和临床研究人员 （LCCC）财团机构。该计划由1781万美元（1584万美元LCCC-DC，197万美元LCCC-NJ）资助， 研究经费（年度直接成本），其中130万美元（LCCC-DC 98万美元，LCCC-NJ 32万美元）经过同行评审 86万美元（54万美元LCCC-DC，32万美元LCCC-NJ）由NCI资助。教统会成员发表了578篇论文，其中 137例为高影响（影响因子[IF] ≥ 8）; 15%为方案间，23%为方案内，48%涉及 与其他NCI指定的癌症中心进行外部合作。ET成员使用所有九个LCCC共享 资源ET解决了华盛顿DC和周边县LCCC集水区的挑战 （LCCC-DC）和卑尔根县，新泽西（LCCC-NJ）通过关注相对 过度代表，如胰腺癌和肺癌，并提供研究启发的癌症护理， 病人，包括服务不足的少数民族，在整个这些集水区。

ABSTRACT The overall mission of the Experimental Therapeutics Program (ET) is to reduce the burden of cancer through preclinical and early clinical drug development; determine optimal treatment combinations and sequences; identify prognostic, predictive and surrogate markers of efficacy and resistance for active agents and deliver best practices to our catchment area and nationally through strategic collaborations. ET encompasses a combination of preclinical, translational and clinical research, with strong ties to the other programs (Breast Cancer [BC], Cancer Prevention and Control [CPC] and Molecular Oncology [MO]). Given its clinical focus, ET has evolved in concert with recent trends and discoveries that have had an impact in the clinic, such as immunotherapy and precision medicine. Aim 1 is focused on targeting known driver pathways of cancer. Aim 2 is focused on targeting the tumor microenvironment (TME) and the immune system. Aim 3 is focused on developing drugs and biomarkers for cancer diagnosis, prognosis and therapy. Significant accomplishments include completing an investigator-initiated trial (IIT) demonstrating the efficacy of pembrolizumab in thymic carcinoma that is shifting the treatment paradigm and work demonstrating the molecular determinants of immune resistance that are identifying new targets for immunotherapy. ET is led by Giuseppe Giaccone, MD, PhD, former Chief of the National Cancer Institute (NCI) Oncology Branch and a leading expert in lung cancer and experimental therapeutics, and Anton Wellstein, MD, PhD, a pharmacologist whose translational research is focused on tumor stromal interactions and mechanisms of cancer progression to metastasis. The LCCC Consortium is comprised of Georgetown Comprehensive Cancer Center, based in Washington, DC (LCCC-DC) and the John Theurer Cancer Center of Hackensack Meridian Health, based in Hackensack, NJ (LCCC-NJ). Accordingly, the LCCC catchment area is defined by the LCCC-DC and LCCC-NJ catchment areas. ET has 43 members, including translational and clinical researchers, from six departments across the Lombardi Comprehensive Cancer Center (LCCC) consortium institutions. The program is funded by $17.81M ($15.84M LCCC-DC, $1.97M LCCC-NJ) in research funding (annual direct costs) of which $1.3M ($0.98M LCCC-DC, $0.32M LCCC-NJ) is peer-reviewed and $0.86M ($0.54M LCCC-DC, $0.32M LCCC-NJ) is NCI funded. ET members published 578 papers, of which 137 were high impact (impact factor [IF] ≥ 8); 15% interprogrammatic, 23% intraprogrammatic and 48% involving external collaborations with other NCI-designated cancer centers. ET members use all nine LCCC Shared Resources. ET addresses challenges in LCCC’s catchment areas in Washington DC and surrounding counties (LCCC-DC) and Bergen County, New Jersey (LCCC-NJ) by focusing on diseases that are relatively overrepresented, such as pancreatic cancer and lung cancer, and offering research-inspired cancer care to patients, including underserved minorities, throughout these catchment areas.