Advancing colorectal cancer management through clinical proteomics: from genotype to proteotype toward clinical translation

INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, with outcomes depending on the stages at diagnosis. Genomic and transcriptomic classifications are largely inferential because the genotype-phenotype relationship is non-linear and is influenced by post-translational regulation, protein turnover, and the tumor microenvironment (TME). Proteomics measures this functional layer directly. AREAS COVERED: This review surveys proteomic technologies for CRC emphasizing mass spectrometry, affinity- and aptamer- based multiplex platforms, post-translational modification proteomics, spatial proteomics, AI-driven structural and predictive analysis, and multi-omics integration. Each platform is evaluated based on clinical questions, the supporting evidence and the barriers to implementation. Literature was drawn primarily from PubMed/MEDLINE and Scopus (2020-2026), emphasizing advanced and translational applications. EXPERT OPINION: Alongside approved blood cfDNA and stool-RNA molecular tests, proteomics is a functional complementary technology that may improve biological interpretation, assay triage and treatment response prediction, although prospective clinical utility remains to be established. The decisive barriers are standardized biospecimens, validation evidence, clinical utility data and interoperable public data sharing. (169 words).