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 ph...