Recent advances in cancer-associated fibroblasts in colorectal cancer: functional subtypes, spatiotemporal dynamics and therapeutic targets.

Abstract

Colorectal cancer (CRC) is a malignant tumour with an extremely high global incidence rate; its development and progression are closely linked to fibroblasts within the tumour microenvironment (TME). In recent years, single-cell and spatial multi-omics technologies have revealed the high heterogeneity of fibroblasts in colorectal cancer and identified multiple subtypes with either oncogenic or tumour-suppressive functions. Within the TME, these fibroblast states have been associated with key processes in tumour initiation, progression, metastasis, and treatment resistance, although direct functional evidence for many of them remains to be established. This review provides a comprehensive overview of the origins, differentiation and activation trajectories, stage-associated distribution patterns, and spatial characteristics of fibroblasts, with a focus on newly identified functional states and their distributions across primary and metastatic CRC. Furthermore, given that the efficacy of current clinical treatments for fibroblasts remains less than satisfactory, there is still a need to develop effective targeted therapies for these newly identified subtypes in the future.