Developing Diagnostic and Therapeutic Strategies to Reduce Hispanic Cancer Disparities Using Genetic, Molecular and Physiological Signatures from Mexican origin Cancer Patients

摘要 拉美裔是美国最大和增长最快的种族人口，据预测，拉美裔占 到2050年，美国人口的比例将增加到近30%。拉美裔美国人患上与健康有关的明显癌症 在美国，差异和癌症是导致拉美裔美国人死亡的主要原因。尽管有相当多的癌症 在与健康相关的问题上，拉美裔在两个重要领域的癌症研究中代表性不足。首先，在那里 很少有研究集中于了解西班牙裔的遗传、分子和生理异常 癌症组织，这对于解释拉美裔癌症健康差异可能特别重要。第二，那里 缺乏拉美裔患者的癌症组织，是开发有针对性的目标的严重障碍 治疗性干预。本研究计划的目标将直接涉及其中的每一个 通过建立第一个全面的墨西哥起源癌症组织生物库和通过 首次开发主要源于墨西哥的新的遗传、分子和细胞特征 将癌症患者作为提供诊断和治疗策略信息的平台。我们对墨西哥起源的关注 人口源于这样一个事实，即美国埃尔帕索德克萨斯州/华雷斯CH MX Borderplex是最具活力的 世界上的国际边界，有250多万人口。德克萨斯州埃尔帕索县 82%的居民是西班牙裔，其中96%是墨西哥裔。拟议中的研究将检验这部小说 假设减少和消除墨西哥血统个体的癌症健康差异是 依赖于识别、理解和治疗-针对独特的分子、基因和 这些患者的癌症的生理特征。具体目标1专注于建立第一个 得克萨斯大学埃尔帕索分校(UTEP)综合墨西哥起源癌症组织生物库 通过我们与埃尔帕索和华雷斯CHMX地区医院建立的合作。这将允许 当地调查人员出于调查目的获取拉美裔癌症患者样本。特定目标2将 解决拉美裔在癌症研究和临床试验中代表性不足的问题。临床观察 如存活率低可能归因于缺乏未知的基因异常。因此，我们建议 利用全面的多重蛋白质组分析和整个外显子组进行第一次FDA批准的药物分析 对从墨西哥起源生物库获得的患者样本进行测序(WES)。具体目标3将 使用分子、多组学和生物信息学方法开发第一批诊断工具，以解决 在西班牙裔社区中，肝癌和前列腺癌的发病率不断上升。目前的研究结果将 通过提供新的见解和方向，对该领域产生持续而强大的影响，以减少 癌症对墨西哥裔拉美裔的有害影响，并将建立UTEP BBRC和EL Paso/Juarez Borderplex作为西班牙裔癌症健康差异研究的关键驱动因素。

ABSTRACT Hispanics are the largest and fastest growing US ethnic demographic, and it is projected that the Hispanic share of the US population will increase to nearly 30% by 2050. Hispanics suffer from marked cancer health-related disparities and cancer is the leading cause of death for Hispanics in the US. Despite these considerable cancer health-related issues, Hispanics are underrepresented in cancer research in two significant areas. First, there is little research focused on understanding the genetic, molecular, and physiological aberrations in Hispanic cancer tissue, which may be particularly important for explaining Hispanic cancer health disparities. Second, there is a lack of availability of cancer tissue from Hispanic patients, a profound barrier for developing targeted therapeutic interventions. The objectives of the present Research Plan will directly address each of these deficiencies by establishing the first comprehensive Mexican Origin Cancer Tissue Biorepository and by developing, for the first time, novel genetic, molecular, and cellular signatures from primarily Mexican origin cancer patients as platforms to inform diagnostic and therapeutic strategies. Our focus on the Mexican origin population stems from the fact that the El Paso TX USA/Juárez CH MX borderplex is one of the most dynamic international borders in the world, with a population of more than 2.5 million residents. In El Paso County, TX 82% of residents are Hispanic, 96% of whom are of Mexican origin. The proposed studies will test the novel HYPOTHESIS that the reduction and elimination of cancer health disparities in Mexican origin individuals is dependent on identifying, understanding, and therapeutically-targeting the unique molecular, genetic and physiological signatures of cancer from these patients. Specific Aim 1 is focused on establishing the first comprehensive Mexican Origin Cancer Tissue Biorepository at The University of Texas at El Paso (UTEP) through our established collaborations with area hospitals in El Paso and Ciudad Juarez CH MX. This will allow local investigators access to Hispanic cancer patient samples for investigative purposes. Specific Aim 2 will address the fact that Hispanics are underrepresented in cancer research and clinical trials. Clinical observations such as poor survival may be attributed to a lack of unknown genetic abnormalities. Therefore, we propose to perform the first FDA-approved drug assay with comprehensive multiplex proteomic analysis and Whole Exome Sequencing (WES) on patient samples obtained from the Mexican Origin Biorepository. Specific Aim 3 will develop the first diagnostic tools using molecular, multi-omics, and bioinformatic approaches to address the growing incidences of liver and prostate cancer within the Hispanic community. The current research findings will exert a sustained and powerful influence on the field by providing novel insight and direction for reducing the deleterious effects of cancer in Hispanics of Mexican origin, and will establish The UTEP BBRC and the El Paso/Juarez borderplex as critical drivers of Hispanic cancer health disparities research.