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Cancer-associated fibroblasts: overview, progress, challenges, and directions

A Correction to this article was published on 28 June 2021

This article has been updated

Abstract

Tumors are one of the main causes of death in humans. The development of safe and effective methods for early diagnosis and treatment of tumors is a difficult problem that needs to be solved urgently. It is well established that the occurrence of tumors involves complex biological mechanisms, and the tumor microenvironment (TME) plays an important role in regulating the biological behavior of tumors. Cancer-associated fibroblasts (CAFs) are a group of activated fibroblasts with significant heterogeneity and plasticity in the tumor microenvironment. They secrete a variety of active factors to regulate tumor occurrence, development, metastasis, and therapeutic resistance. Although most studies suggest that CAFs have significant tumor-promoting functions, some evidence indicates that they may have certain tumor-suppressive functions in the early stage of tumors. Current research on CAFs continues to face many challenges, and the heterogeneity of their origin, phenotype, and function is a major difficulty and hot spot. To provide new perspectives for the research on CAFs and tumor diagnosis and treatment, this review summarizes the definition, origin, biomarkers, generation mechanism, functions, heterogeneity, plasticity, subpopulations, pre-metastasis niches (PMN), immune microenvironment, and targeted therapy of CAFs, describes the research progress and challenges, and proposes possible future research directions based on existing reports.

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Fig. 1: The origin, activating factors, subpopulations, secretome or potential biomarkers, and functions of CAFs are complex, diverse, and heterogeneous.

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Acknowledgements

The authors thank Xin Cheng for her assistance in illustrating the schematic figure.

Funding

This review was supported by grants from the National Natural Science Funds of China (grant no. 82060536); Open Project from the Tumor Immunization and Prevention Key Experiment Laboratory of Yunnan Provincial (grant no. 2017DG004-04); Scientific Research Fund from the Education Department of Yunnan Provincial (grant no. 2020J0218); and the Health Science and Technology Talent Training Project of Kunming city (grant no. 2020-SW-12).

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Ping, Q., Yan, R., Cheng, X. et al. Cancer-associated fibroblasts: overview, progress, challenges, and directions. Cancer Gene Ther 28, 984–999 (2021). https://doi.org/10.1038/s41417-021-00318-4

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