University of California and UT Southwestern D-PDTC

加州大学和 UT 西南 D-PDTC

基本信息

批准号：
10733391
负责人：
Luis Guillermo Carvajal Carmona
金额：
$ 106.11万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10733391
关键词：
Advanced Malignant Neoplasm Affect Asian Asian ancestry Asian population Bioinformatics Biological Biological Process California Cancer Biology Cancer Center Cancer Model Cancer Therapy Evaluation Program Catchment Area Cause of Death Cell Cycle Cells Clinical Clinical Trials Collection Combination Drug Therapy Combined Modality Therapy Complex Comprehensive Cancer Center Data Decision Making Development Digit structure Disease Disparity Drug Combinations Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor FDA approved FRAP1 gene Family Female Frequencies Genetic Genome Genomics Goals Grant Health Disparities Research Implant Indigenous American Infrastructure Latina Population Latino Latino Population Light Los Angeles Lung Neoplasms Malignant Neoplasms Malignant neoplasm of lung Minority Minority Groups Modeling Molecular Molecular Abnormality Mutate Mutation Oncogenes PI3K/AKT Pathway interactions Patient Isolation Patients Pharmaceutical Preparations Phosphotransferases Pilot Projects Population Population Heterogeneity Pre-Clinical Model Precision Health Precision therapeutics Preclinical Drug Development Preclinical Testing Process Productivity Publishing Regimen Research Research Personnel Research Project Grants Resistance Resources Risk Factors Role San Francisco Signal Transduction Site Smoking Smoking History Solid Stomach Stomach Neoplasms Testing Texas Time Translating Underrepresented Minority Universities Woman Work cancer diagnosis cancer health disparity cancer subtypes comparative effective therapy ethnic diversity ethnic minority expectation health equity malignant stomach neoplasm member minority patient molecular subtypes mortality mortality disparity multidisciplinary mutant never smoker new therapeutic target novel patient derived xenograft model people of color precision oncology racial diversity racial minority resistance mechanism response response biomarker targeted cancer therapy targeted treatment therapeutically effective treatment response tumor tumor diagnosis tumorigenesis

项目摘要

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.

项目概要/摘要加州大学和德克萨斯大学西南分校 (UCaTS) 患者衍生的多样性异种移植 (PDX) 开发和试验中心是一项注重多样性的赠款，其目标是建立和描述了来自种族和民族不同人群的至少 120 个新 PDX 的特征，并将这些 PDX 用作临床前模型，以更好地了解肿瘤发生机制，测试 FDA 批准的和 NCI-CTEP 单药和药物联合疗法并推进癌症健康差异研究。我们正在进行的加州大学患者衍生和试验中心 (UCaMP, 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], 加州大学欧文分校 Chao Family 综合癌症中心 (UCI)、加州大学洛杉矶分校琼森综合癌症中心 (UCLA)、加州大学圣地亚哥分校摩尔斯癌症中心（UCSD）、加州大学旧金山分校海伦迪勒家庭综合癌症中心（UCSF）和大学德克萨斯州西南 Harold C. Simmons 癌症中心 (UTSW) 总共包括一个团队。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研究人员差异、临床试验开发、生物信息学和大型多中心管理将实现。其目标是通过两个研究项目项目 1——“推进拉丁裔胃癌精准医学”。通过源自患者的模型”专注于为大多数人开发新颖、有效的治疗方案通常可药物化且基因组复杂的拉丁裔 GC 亚型，涉及多种共突变途径（如细胞周期激酶、PI3K/AKT/mTOR、WNT 和 RTK-RAS）并研究耐药机制靶向治疗，确定反应生物标志物并评估血统如何影响反应项目 2 –。 “精确靶向差异相关的 EGFR 突变肺肿瘤，以避免早期对 EGFR 的耐药性抑制剂”，重点关注少数群体中最常见的肺癌 (LC) 亚型之一，EGFR- 这种分子亚型在女性肺癌中占很大比例。该项目将利用 PDXNet 和我们的 UCaTS 肺癌 PDX 专业知识。和资源，与 FDA 批准的药物和 NCI-CTEP 药物一起开发有效的靶向治疗组合寻求克服 EGFR-TKI 的早期耐药性。