JMIR Publications

ABSTRACT

Colorectal cancer (CRC) ranks as the third most diagnosed malignancy globally. Its molecular complexity, driven by genomic alterations, epigenetic modifications, metabolic reprogramming, and microbiome interactions, cannot be fully elucidated through single-omics approaches. Multi-omics integration, combining genomics, transcriptomics, proteomics, metabolomics, and metagenomics, has transformed understanding of CRC biology, enabling comprehensive molecular characterization at unprecedented resolution. These integrated approaches have refined the Consensus Molecular Subtypes classification, identified biomarkers for early detection and prognostic stratification, and revealed therapeutically actionable vulnerabilities. Multi-omics strategies are reshaping precision oncology by establishing mechanistic links between molecular profiles and clinical outcomes, guiding patient selection for immunotherapy in microsatellite instability-high and mismatch repair-deficient tumors, and elucidating resistance mechanisms. Integration with artificial intelligence, single-cell sequencing, spatial transcriptomics, and liquid biopsy has accelerated clinical translation. However, challenges persist in data standardization, computational integration, multicenter validation, and cost-effective implementation. This review synthesizes recent multi-omics CRC research advances, examines translational applications, evaluates current challenges, and outlines strategic priorities for implementing integrative approaches in routine practice. Successful translation requires international collaboration, harmonized data repositories, and clinical trials evaluating multi-omics-guided strategies.