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

摘要 西班牙裔是美国人口中最大和增长最快的种族，预计西班牙裔的份额 到2050年，美国人口将增加到近30%。西班牙裔人患有与健康有关的明显癌症 在美国，癌症是西班牙裔美国人的主要死因。尽管这些癌症 在健康相关问题上，西班牙裔在两个重要领域的癌症研究中代表性不足。一是 很少有研究集中在理解西班牙裔美国人的遗传、分子和生理畸变上， 癌症组织，这可能是解释西班牙裔癌症健康差异特别重要。二是 缺乏西班牙裔患者的癌症组织，这是开发靶向治疗的一个严重障碍。 治疗干预。本研究计划的目标将直接解决这些问题 通过建立第一个全面的墨西哥起源癌症组织生物储存库， 首次开发出主要来自墨西哥的新型遗传、分子和细胞特征 癌症患者作为平台，告知诊断和治疗策略。我们对墨西哥起源的关注 人口源于这样一个事实，即埃尔帕索TX美国/华雷斯CH MX边境是最具活力的 世界上的国际边界，拥有超过250万居民的人口。位于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。拟议中的研究将测试小说 假设减少和消除墨西哥裔个体的癌症健康差异是 依赖于识别、理解和治疗靶向独特的分子、遗传和 癌症的生理特征具体目标1是建立第一个 德克萨斯大学埃尔帕索分校（UTEP）的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城CH MX地区医院的合作。这将允许 当地研究人员出于研究目的访问西班牙裔癌症患者样本。具体目标2将 解决西班牙裔在癌症研究和临床试验中代表性不足的问题。临床观察结果 如生存率低可能是由于缺乏未知的遗传异常。因此，我们建议 通过全面的多重蛋白质组学分析和全外显子组分析，进行首个FDA批准的药物检测 对从墨西哥原产地生物储存库获得的患者样品进行测序（WES）。第3章将 开发第一个诊断工具，使用分子，多组学和生物信息学方法来解决 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，减少 癌症的有害影响，在西班牙裔墨西哥人的起源，并将建立UTEP BBRC和El 帕索/华雷斯边境是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.