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.

项目摘要/摘要加利福尼亚大学和德克萨斯大学西南（UCATS）多样性患者衍生异种移植（PDX）开发和试验中心是一项以多样性为中心的赠款，其目的是建立和表征至少120个来自大致和种族多样性种群的新PDX，并将这些PDX用作临床前模型更好地了解肿瘤发生的机制，以测试FDA批准和NCI-CTEP 单药和药物组合疗法并提高癌症健康差异研究。扩展我们正在进行的加利福尼亚大学患者衍生和试验中心的现有PDX基础设施（UCAMP，UCAMP， U54CA233306），UCAT已完成六个NCI指定的综合癌症中心（CCC）：UC Davis 综合性癌症中心（UCD）[领导机构]，加州大学欧文（UC）（UCI），加州大学洛杉矶分校乔恩森综合癌症中心（UCLA），加州大学圣地亚哥摩尔斯癌症中心（UCSD），加州大学旧金山分校海伦·迪勒（Helen Diller）家庭综合癌症中心（UCSF）和大学德克萨斯州西南哈罗德·C·西蒙斯癌症中心（UTSW）。 UCAT共同包括一个团队跨学科研究人员在PDX开发，临床前药物测试，癌症健康方面具有优势差异，临床试验发展，生物信息学和大型多中心给药。 UCAT将实现它通过两个研究项目的目标。项目1 - “在拉丁美洲裔胃癌精密医学通过患者衍生的建模”的重点是开发大多数新型，有效的治疗方案通常是可吸毒和基因复杂的拉丁裔GC亚型途径（例如细胞周期激酶，PI3K/AKT/MTOR，WNT和RTK-RAS），并研究耐药机制为了靶向疗法，确定反应生物标志物并评估祖先如何影响反应。项目2 - “精确靶向差异相关的EGFR突变肺肿瘤以避免早期抵抗EGFR 抑制剂”，重点是少数民族中最常见的肺癌（LC）亚型之一，EGFR- 突变的肺肿瘤。该分子亚型代表女性肺癌诊断的高比例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专业知识以及与FDA批准和NCI-CTEP代理开发有效的有针对性治疗组合的资源试图克服对EGFR-TKIS的早期抵抗。