From laboratory bench to surgical room: Molecular profiling and single-cell technologies in precision surgery for...

Colorectal cancer (CRC) represents one of the major global health challenges, ranking among the top three leading causes of cancer-related mortality. Over the past decade, remarkable advances in molecular oncology, cancer genetics, and high-resolution single-cell technologies have reshaped the clinical landscape, refining prognostic frameworks and enabling new therapeutic opportunities. CRC is recognized as a heterogeneous disease driven by multiple pathways, including chromosomal instability (CIN), microsatellite instability (MSI), and the CpG island methylator phenotype (CIMP). These canonical classification models have been expanded through whole-genome sequencing, which has allowed the identification of novel driver mutations, mutational signatures linked to environmental exposures as well as immune escape mechanisms with translational significance. The Consensus Molecular Subtypes (CMS) framework, along with the growing recognition of the importance of tumour location (sidedness), has influenced patient stratification and systemic treatment choice. At the same time, liquid biopsy technologies and organoid platforms have transformed preclinical modelling and perioperative surveillance. In this context, single-cell sequencing and spatial multi-omics have provided unprecedented resolution of intra-tumoral heterogeneity, stromal-immune crosstalk, and clonal dynamics during therapy, with direct implications for surgical oncology. This review synthesizes recent advances in CRC biology, highlights translational opportunities of organoid and single-cell technologies, and discusses their integration into perioperative strategies to support the concept of precision surgical in oncology. These advances increasingly position surgical resection as the final integrative step in translational oncology, where molecular profiling and functional modelling guide informed patient selection, operative timing, and perioperative treatment strategies.