University of California and UT Southwestern D-PDTC

项目摘要/摘要 加州大学和德克萨斯大学西南分校(UCATS)患者来源的多样性 异种移植(PDX)开发和试验中心是一项专注于多样性的赠款，目标是建立和 描述至少120个来自不同种族和民族人群的新的PDX，并将这些PDX用作 临床前模型，以更好地了解肿瘤发生的机制，测试FDA批准的和NCI-CTEP 单一药物和药物联合治疗，并推进癌症健康差异研究。扩展 我们正在进行的加州大学患者衍生和试验中心(UCaMP)的现有PDX基础设施 U54CA233306)，UCATS由六个NCI指定的综合癌症中心(CCC)组成：加州大学戴维斯分校 综合癌症中心(UCD)[牵头机构]，加州大学欧文·赵家族综合癌症中心 (UCI)、加州大学洛杉矶分校强森综合癌症中心(UCLA)、加州大学圣地亚哥·摩尔癌症中心 加州大学洛杉矶分校(UCSD)、加州大学旧金山分校海伦·迪勒家庭综合癌症中心(UCSF)和加州大学 德克萨斯州西南部哈罗德·C·西蒙斯癌症中心(UTSW)。总体而言，UCATS包括一支 在PDX开发、临床前药物测试、癌症健康方面具有优势的跨学科调查人员 差异、临床试验开发、生物信息学和大型多中心管理。UCATS将实现 它的目标是通过两个研究项目。项目1--“在拉丁裔中推进胃癌精准医学 通过患者衍生模型“致力于为大多数人开发新的、有效的治疗方案 常见的可用药和基因复杂的拉丁裔GC亚型，涉及多个 细胞周期蛋白激酶、PI3K/AKT/mTOR、WNT和RTK-RAS等途径，研究耐药机制 对于靶向治疗，确定应答生物标记物，并评估祖先如何影响应答。项目2-- 精确靶向差异相关的EGFR突变肺癌以避免对EGFR的早期耐药 抑制物“，专注于少数族裔人群中最常见的肺癌(LC)亚型之一，EGFR- 突变的肺部肿瘤。这种分子亚型在女性确诊的肺癌中所占比例很高。 拉丁裔和亚洲血统的患者。该项目将利用PDXNet和我们的UCATS肺癌PDX专业知识 和资源，以开发与FDA批准的和NCI-CTEP药物的有效靶向治疗组合 寻求克服对EGFR-TKIs的早期耐药性。

PROJECT SUMMARY/ABSTRACT The University of California and the University of Texas Southwestern (UCaTS) Diversity Patient-Derived Xenograft (PDX) Development and Trial Center’s is a diversity-focused grant with a goal of establishing and characterizing at least 120 new PDXs from racially and ethnically diverse populations and use these PDXs as preclinical models to better understand the mechanisms of oncogenesis, to test FDA-approved and NCI-CTEP single agent and drug combination therapies and to advance cancer health disparities research. Expanding the existing PDX infrastructure from our ongoing University of California Patient Derived and Trial Center (UCaMP, U54CA233306), UCaTS is comprised of six NCI-designated Comprehensive Cancer Centers (CCC): UC Davis Comprehensive Cancer Center (UCD) [lead institution], UC Irvine Chao Family Comprehensive Cancer Center (UCI), UC Los Angeles Jonsson Comprehensive Cancer Center (UCLA), UC San Diego Moores Cancer Center (UCSD), UC San Francisco Helen Diller Family Comprehensive Cancer Center (UCSF), and the University of Texas Southwestern Harold C. Simmons Cancer Center (UTSW). Collectively, UCaTS includes a team of transdisciplinary investigators with strengths in PDX development, preclinical drug testing, cancer health disparities, clinical trial development, bioinformatics, and large multicenter administration. UCaTS will achieve its goal through two Research Projects. Project 1 – “Advancing gastric cancer precision medicine in Latinos through patient-derived modeling” focuses on developing novel, effective therapeutic regimens for most commonly druggable and genomically complex Latino GC subtype, which involves co-mutations in multiple pathway (such as cell cycle kinase, PI3K/AKT/mTOR, WNT and RTK-RAS) and to study resistance mechanisms to targeted therapies, identify response biomarkers and assess how ancestry influences response. Project 2 – “Precision targeting of disparity-associated EGFR mutant lung tumors to circumvent early resistance to EGFR inhibitors”, focuses on one of the most common lung cancer (LC) subtypes in minority populations, EGFR- mutated lung tumors. This molecular subtype represents a high proportion of lung cancer diagnosed in female patients of Latino and Asian ancestry. The project will utilize PDXNet and our UCaTS lung cancer PDX expertise and resources to develop effective targeted therapy combinations with FDA-approved and NCI-CTEP agents seeking to overcome early resistance to EGFR-TKIs.