Adopting a functional precision medicine approach to reduce cancer disparities in Hispanic and Black children of Miami

FIU-RCMI研究项目#1摘要 尽管儿童癌症的总生存期有所改善，但种族/民族之间的治疗差异仍然存在。 与非西班牙裔白人相比。黑人或西班牙裔种族/民族都显著相关 儿童肉瘤、脑和中枢神经系统肿瘤的总体生存率降低。 因此，对于减少种族/民族差异以改善检测、治疗和预后，存在大量未满足的需求。 儿童癌症患者的生存率。有充分的证据表明，患有癌症的西班牙裔和黑人儿童 参加癌症治疗临床试验的可能性比非西班牙裔白色人低50%以上 孩子特别是，提供精确肿瘤学方法的研究大大低估了种族和 少数民族人口。因此，必须提供精确的肿瘤学研究， 来自不同种族和民族背景的儿童，以便收集有意义的精确数据， 个人可能受益于癌症研究的突破和个性化治疗。我们建议 通过首次采用功能性精准医学（FPM）方法来解决这些问题， 个别少数民族患者了解遗传，分子，转录组学和表型特性 这对于解释西班牙裔和黑人癌症健康差异可能特别重要。我们 假设西班牙裔和黑人群体中不同遗传变异可能实质上有助于 药物治疗反应和总生存率的变异性。使用我们强大的高通量离体药物 敏感性试验（DST），并结合突变分析，我们将能够创建一个纲要， 个体患者的药物反应，将可操作的突变与选择性靶向治疗相匹配， 临床上对无其他选择的难治性患者进行个体化治疗。因此，我们建议 具体目标1：评价功能性精准医学（FPM）方法作为一种工具， 减少儿童患癌症的差异。我们打算扩大个性化治疗选择的可及性， 基于离体药物的西班牙裔和黑人儿科癌症患者的临床管理建议 敏感性测试（DST）和基因组分析。具体目标2：揭示遗传学之间的新相关性 改变和离体药物反应在少数群体。我们将进行多组学分子分析 并整合机器学习平台，以揭示分子改变与 有效的药物，特别是与西班牙裔和黑人儿科人群。我们的研究将是第一个 以证明FPM在改善患者结局和减少或消除 南佛罗里达西班牙裔和黑人儿童的癌症差异。我们提出的工作还将导致 识别与少数群体相关的独特遗传和表型特性，提供 个性化干预措施的机会，以促进健康公平和更有效的癌症治疗。

FIU-RCMI Research Project #1 Abstract Despite improvements in overall survival for pediatric cancers, treatment disparities remain for racial/ethnic minorities compared to non-Hispanic Whites. Black or Hispanic race/ethnicity are both significantly associated with decreased overall survival outcomes in childhood sarcomas, brain, and central nervous system tumors. Thus, there is a large unmet need for reducing racial/ethnic disparities to improve detection, treatment, and survival in pediatric cancer patients. It is well documented that Hispanic and Black children with cancer are more than 50 percent less likely to enroll in clinical trials testing cancer treatments than non-Hispanic White children. Particularly, studies that provide precision oncology approaches vastly underrepresent racial and ethnic minority populations. Thus, it is imperative to provide precision oncology studies that encompass children from diverse racial and ethnic backgrounds, so that meaningful precision data can be collected, and all individuals may benefit from cancer research breakthroughs and personalized treatments. We propose to address these problems by adopting, for the first time, a functional precision medicine (FPM) approach for individual minority patients to understand the genetic, molecular, transcriptomic, and phenotypic properties which may be particularly important for explaining Hispanic and Black cancer health disparities. We hypothesize that distinct genetic variance in Hispanic and Black populations is likely to substantially contribute to variability in drug treatment response and overall survival. Using our robust high throughput ex vivo drug sensitivity assay (DST), and combining it with mutation analysis, we will be able to create a compendium of drug responses in individual patients, match actionable mutations with selective targeted therapies, and clinically apply individual treatment to refractory patients with no alternative options. Hence, we propose the following aims: Specific Aim 1: To evaluate a functional precision medicine (FPM) approach as a tool to reduce cancer disparities in children. We intend to expand access of personalized treatment options and clinical management recommendations to Hispanic and Black pediatric cancer patients based on ex vivo drug sensitivity testing (DST) and genomic profiling. Specific Aim 2: To uncover novel correlations between genetic alterations and ex vivo drug responses in minority populations. We will perform multi-omics molecular profiling and integrate a machine learning platform to uncover novel relationships between molecular alterations and effective drugs specifically associated with Hispanic and Black pediatric populations. Our study will be the first of its kind to demonstrate the clinical utility of FPM to improve patient outcomes and reduce or eliminate the cancer disparities in Hispanic and Black children of South Florida. Our proposed work would also lead to identifying unique genetic and phenotypic properties associated with minority populations, providing opportunities for personalized interventions to promote health equity and more effective cancer treatments.