ABSTRACT: ENGAGEMENT OPTIMIZATION UNIT (EOU) With advances in molecular genomics, we have an improved understanding of the drivers of tumor evolution and therapy response, yet inclusion of Hispanic/Latino CRC patients in these studies has been minimal. Moreover, there are virtually no empirical data to inform best practices for educating, consenting, enrolling and retaining H/L patients in cancer genomics investigations, nor are there culturally, language, literacy and numeracy appropriate tools to utilize to reach these patients or to facilitate interpretation of data they receive. A better understanding of how H/Ls understand, value and communicate genomics-related information is the essential foundation for rigorous research to optimize patient engagement and outcomes. The Engagement Optimization Unit (EOU) will fill these gaps by conducting rigorous research to generate evidence-based best practices and by validating culturally specific tools for optimizing Hispanic/Latino patient engagement and empowerment. This will be accomplished via an iterative process of experimentation, evaluation, implementation and re-evaluation in a study population at LAC+USC and Norris of 275 H/L participants with metastatic CRC, as well as a separate cohort of 500 H/L participants with CRC (both newly diagnosed and survivors) who will be engaged in genomic sequencing and follow up. The Specific Aims are: (1) to assess the educational and communication needs of H/L CRC patients related to participation in cancer genomics research; and evaluate the role of language, acculturation, numeracy and health literacy; (2) to develop best practices for engagement of H/L CRC patients in informed consent for genomic characterization; (3) to determine the most efficacious strategies to communicate genomic results to H/L CRC patients; and (4) to develop and test a comprehensive tool kit (The Hispanic/Latino Genomic Engagement through Narrative Empowerment Tool Kit (H/L G.E.N.E.)) for use by promotores de salud (community health workers) and other providers with the purpose of optimizing H/L engagement, enhancing recruitment and strengthening retention of H/L patients into cancer genomics research.