University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center (UCaMP) to Reduce Cancer Health Disparities

加州大学少数族裔患者异种移植物 (PDX) 开发和试验中心 (UCaMP) 旨在减少癌症健康差异

• 批准号: 10011077
• 负责人: Luis Guillermo Carvajal Carmona
• 金额: $ 1.2万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011077
• 关键词: Abbreviations; Achievement; Address; Advanced Malignant Neoplasm; Affect; African American; American; Asian Americans; Bioinformatics; Biological; Biological Markers; Bladder Neoplasm; California; Cancer Model; Cell Cycle Regulation; Censuses; Clinical; Clinical Trials; Collaborations; Color; Comprehensive Cancer Center; Data; Decision Making; Development; Drug Combinations; FRAP1 gene; Family; Funding; Future; Genes; Genetic; Genetic Variation; Goals; Health; Hispanics; Histologic; Individual; Infrastructure; Institutional Review Boards; Investigational Drugs; Latino; Liver neoplasms; Los Angeles; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of liver; Malignant neoplasm of lung; Malignant neoplasm of urinary bladder; Minority; Mission; Mutate; Mutation; Native Hawaiian; Not Hispanic or Latino; PI3K/AKT; Pacific Island Americans; Pathway interactions; Patients; Peer Review; Pharmacotherapy; Pilot Projects; Population; Precision therapeutics; Preclinical Testing; Primary Malignant Neoplasm of Liver; Regimen; Research; Research Personnel; Research Project Grants; Research Support; Resistance; Resources; Risk Factors; San Francisco; Site; Smoking; Squamous Cell Lung Carcinoma; Stomach Neoplasms; System; Testing; Translating; Treatment Efficacy; Universities; Xenograft Model; Xenograft procedure; cancer health disparity; clinical decision-making; cohesion; comparative; drug testing; ethnic diversity; ethnic minority population; health disparity; inhibitor/antagonist; malignant stomach neoplasm; member; novel; precision oncology; racial and ethnic; resistance mechanism; response; risk sharing; targeted cancer therapy; targeted treatment; therapy development; treatment disparity; treatment response; tumor

OVERALL University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center (UCaMP) to Reduce Cancer Health Disparities PROJECT SUMMARY/ABSTRACT The goal of UCaMP is to establish and characterize at least 200 patient-derived cancer xenografts (PDXs), and utilize these PDXs in preclinical testing of single agents and drug combinations that help guide future clinical decision-making emphasizing the largest racial/ethnic minority populations residing in California: Hispanic/Latino Americans [HLAs], Asian American/Native Hawaiian/Pacific Islander [AANHPIs], and African American [AAs] compared to Non-Hispanic Whites [NHWs]. We have established an accomplished transdisciplinary research team with an outstanding infrastructure that includes a University of California-wide central IRB system called Reliance and strong preliminary data to support the proposed PDX and cancer disparities research, thus allowing our results to be easily translated to clinical trials. UCaMP is comprised of four University of California NCI-designated Comprehensive Cancer Centers: UC Davis Comprehensive Cancer Center (UC Davis), UC Los Angeles Jonsson Comprehensive Cancer Center (UCLA), UC Irvine Health Chao Family Comprehensive Cancer Center (UC Irvine), and UC San Francisco Helen Diller Family Comprehensive Cancer Center (UCSF). Our collective strengths include complementary expertise in PDX development and drug testing, cancer health disparities, and clinical trial development robustly supported by cores for PDX, Pilot Studies, Bioinformatics, and Administration. We will achieve our goal through two Research Projects. Project 1 - Characterizing Treatment Responses with PDX Models for Gastric and Liver Tumors, specifically addresses cancer health disparities in gastric cancers (GC) and liver cancers (LC) that disproportionately affect all racial/ethnic minorities especially in HLA and AANHPI populations. By understanding the genetic and response differences among HLA, AANHPI compared to NHWs, we could enhance the precision of therapeutic treatments, identify resistance-associated biomarkers, and study resistance mechanisms to targeted therapies. Project 2 - Characterizing Treatment Responses with PDX Models for Lung and Bladder Tumors focuses on treatment disparities between AA and NHW patients to identify therapies targeting common genetic alterations (e.g. PI3K pathway) and to reveal targeted therapy resistance mechanisms for lung squamous cell carcinoma (LSCC) and advanced bladder cancer (aBC).

整体 加州大学少数族裔患者衍生异种移植物（PDX）开发和试验中心 （UCaMP）减少癌症健康差异 项目总结/摘要 UCaMP的目标是建立和表征至少200个患者来源的癌症异种移植物（PDX）， 利用这些PDX进行单药和药物组合的临床前测试，帮助指导未来的临床 强调居住在加州的最大种族/少数民族人口的决策： 西班牙裔/拉丁裔美国人[HLAs]、亚裔美国人/夏威夷原住民/太平洋岛民[AANHPIs]和非洲人 美国人[AAs]与非西班牙裔白人[NHWs]相比。我们已经建立了一个成功的 跨学科的研究团队，拥有出色的基础设施，包括加州大学范围内的 中央IRB系统称为Reliance和强大的初步数据，以支持拟议的PDX和癌症 差异研究，从而使我们的结果很容易转化为临床试验。UCaMP由 四个加州大学指定的综合癌症中心：加州大学戴维斯分校综合 癌症中心（加州大学戴维斯分校），加州大学洛杉矶琼森综合癌症中心（加州大学洛杉矶分校），加州大学欧文分校健康 Chao Family Comprehensive Cancer Center（UC Irvine）和UC San弗朗西斯科Helen Diller Family 综合癌症中心（UCSF）。我们的集体优势包括PDX方面的互补专业知识 开发和药物测试，癌症健康差异和临床试验开发得到了 PDX、试点研究、生物信息学和管理的核心。我们将通过两个方面来实现我们的目标 研究项目。项目1 -使用胃和肝脏的PDX模型表征治疗反应 肿瘤，特别是胃癌（GC）和肝癌（LC）的癌症健康差异， 不成比例地影响所有种族/族裔少数群体，特别是HLA和AANHPI人群。通过 了解HLA，AANHPI与NHW之间的遗传和反应差异，我们可以 提高治疗的精确性，识别耐药相关的生物标志物，并研究 对靶向治疗的耐药机制。项目2 -使用PDX表征治疗反应 肺和膀胱肿瘤模型重点关注AA和NHW患者之间的治疗差异， 鉴定针对常见遗传改变（例如PI 3 K通路）的疗法，并揭示靶向疗法 肺鳞状细胞癌（LSCC）和晚期膀胱癌（aBC）的耐药机制。