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

总体来说 加州大学少数民族患者来源的异种移植(PDX)开发和试验中心 (UCaMP)减少癌症健康差距 项目摘要/摘要 UCaMP的目标是建立和鉴定至少200例患者来源的肿瘤异种移植(PDX)，以及 利用这些PDX进行单一药物和药物组合的临床前测试，以帮助指导未来的临床 强调居住在加利福尼亚州的最大种族/少数民族人口的决策： 西班牙裔/拉丁裔美国人[HLA]、亚裔美国人/夏威夷原住民/太平洋岛民[AANHPI]和非洲人 美国人[AA]与非西班牙裔白人[NHW]的比较。我们已经建立了一个有成就的 拥有卓越基础设施的跨学科研究团队，其中包括加州大学 名为Reliance的中央IRB系统和强大的初步数据支持拟议的PDX和癌症 差异研究，从而使我们的结果可以很容易地转化为临床试验。UCaMP由以下内容组成 加州大学国家癌症研究所指定的四个综合癌症中心：加州大学戴维斯综合分校 癌症中心(加州大学戴维斯分校)、加州大学洛杉矶分校琼森综合癌症中心(加州大学洛杉矶分校)、加州大学欧文健康分校 曹氏家庭综合癌症中心(加州大学欧文分校)和加州大学旧金山分校海伦·迪勒家庭 综合癌症中心(UCSF)。我们的集体优势包括在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强有力的支持 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-用胃和肝脏的PDX模型表征治疗反应 肿瘤，特别针对胃癌(GC)和肝癌(LC)之间的癌症健康差异 不成比例地影响所有种族/族裔少数群体，特别是在人类白细胞抗原和AANHPI人群中。通过 了解人类白细胞抗原、AANHPI和NHW之间的遗传和反应差异，我们可以 提高治疗的精确度，识别与耐药相关的生物标志物，并进行研究 靶向治疗的耐药机制。项目2--用PDX表征治疗反应 肺和膀胱肿瘤模型侧重于AA和NHW患者之间的治疗差异 确定针对常见基因改变的治疗方法(例如，PI3K途径)并揭示靶向治疗 肺鳞癌(LSCC)和晚期膀胱癌(ABC)的耐药机制。

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).