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序列； 确定有效药物的疗效和耐药性的预测、预测和替代标记物，并提供最佳 通过战略合作，将这些做法推广到我们的集水区和全国。ET包含一个组合 临床前、转化性和临床研究，与其他项目(乳腺癌[BC]， 癌症预防与控制[CPC]和分子肿瘤学[MO])。鉴于其临床重点，ET已在 与最近在临床上产生影响的趋势和发现相一致，如免疫疗法和 精准医学。AIM 1的重点是针对已知的癌症驱动途径。《目标2》专注于 靶向肿瘤微环境(TME)和免疫系统。AIM 3专注于开发药物和 癌症诊断、预后和治疗的生物标志物。重大成就包括完成 研究人员发起的试验(IIT)证明培溴利珠单抗对正在转移的胸腺癌的疗效 治疗范例和工作展示了免疫耐药的分子决定因素 确定免疫治疗的新靶点。ET由朱塞佩·贾科内领导，医学博士，前首席执行官 国家癌症研究所(NCI)肿瘤学分会，肺癌和实验领域的领先专家 Anton Wellstein，医学博士，药理学家，专注于肿瘤的翻译研究 间质的相互作用和癌症进展到转移的机制。LCCC财团由 总部设在华盛顿特区的乔治敦综合癌症中心(LCCC-DC)和John Theurer 哈肯萨克子午线健康癌症中心，总部设在新泽西州哈肯萨克(LCCC-NJ)。因此，LCCC 集水区由LCCC-DC和LCCC-NJ集水区界定。ET有43个成员，包括 来自隆巴迪综合癌症中心六个科室的翻译和临床研究人员 (LCCC)联合体机构。该计划的资金来自1781万美元(1584万美元LCCC-DC，197万美元LCCC-NJ) 研究资金(年度直接成本)，其中130万美元(LCCC-DC为0.98万美元，LCCC-NJ为32万美元)经过同行审查 860万美元(LCCC-DC为50万美元，LCCC-NJ为32万美元)由NCI提供资金。ET成员发表论文578篇，其中 137个是高影响(影响系数[IF]≥8)；15%是方案间，23%是方案内，48%涉及 与NCI指定的其他癌症中心的外部合作。ET成员使用所有九个LCCC共享 资源。ET解决了LCCC在华盛顿特区和周边县的集水区面临的挑战 (LCCC-DC)和新泽西州卑尔根县(LCCC-NJ)通过关注相对 比例过高，如胰腺癌和肺癌，并提供受研究启发的癌症护理 患者，包括未得到充分服务的少数民族，遍布这些集水区。

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.