CLARITAS: PHENOTYPIC AND MULTI-OMIC READOUTS TO INFORM RARE CANCER COMBINATION THERAPY

Sequence-based precision medicine has transformed our understanding of disease, yet clinical insight remains limited. These challenges underscore a critical need for new approaches that bridge the genotype-phenotype gap. Current methods for studying disease mechanisms and drug effects have significant limitations. Organoids cultivated in microplates face limitations in molecular multiplexing capability. Fixed tissue sections analyzed with spatial-omics techniques are limited to a single time point, preventing the capture of dynamic longitudinal changes in living systems.To overcome these limitations, we propose the development of the Claritas™ platform, a novel 'Phen-omics' approach that integrates top-down phenotypic analysis with bottom-up multi-omics workflows. This platform enables the systematic identification of causal genes driving observed response while allowing researchers to perform large-scale, cost-effective organoid testing.The Claritas™ platform will be applied to addressing the unmet need for combination therapy with rare cancers, an urgent and dire clinical indication. The specific aims include refining the Claritas™ platform for converting organoid samples into mounted sections and validating its effectiveness in predicting effective combination therapy for rare cancers with a 5 year survival rate of less than 50%.