Cancer-associated fibroblasts (CAFs) are an abundant component of the tumor microenvironment and have been shown to possess critical functions in tumor progression. Although their roles predominantly have been described as tumor-promoting, more recent findings have identified subsets of CAFs with tumor-restraining functions. Accumulating evidence underscores large heterogeneity in fibroblast subsets in which distinct subsets differentially impact the initiation, progression, and metastasis of colorectal cancer. In this review, we summarize and discuss the evolving role of CAFs in colorectal cancer, highlighting the ongoing controversies regarding their distinct origins and multifaceted functions. In addition, we explore how CAFs can confer resistance to current therapies and the challenges of developing effective CAF-directed therapies. Taken together, we believe that, in this rapidly evolving field, it is crucial first to understand CAF dynamics comprehensively, and to bridge existing knowledge gaps regarding CAF heterogeneity and plasticity before further exploring the clinical targeting of CAFs.

中文翻译：

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成纤维细胞在协调结直肠肿瘤发生和进展中的作用

癌症相关成纤维细胞（CAF）是肿瘤微环境的丰富组成部分，并已被证明在肿瘤进展中具有关键功能。尽管它们的作用主要被描述为促进肿瘤，但最近的研究结果已经确定了具有抑制肿瘤功能的 CAF 子集。越来越多的证据强调了成纤维细胞亚群的巨大异质性，其中不同的亚群对结直肠癌的发生、进展和转移有不同的影响。在这篇综述中，我们总结并讨论了 CAF 在结直肠癌中不断演变的作用，强调了关于其独特起源和多方面功能的持续争议。此外，我们还探讨了 CAF 如何赋予当前疗法耐药性，以及开发有效的 CAF 导向疗法的挑战。综上所述，我们认为，在这个快速发展的领域，在进一步探索 CAF 的临床靶向之前，首先全面了解 CAF 动态，并弥合有关 CAF 异质性和可塑性的现有知识差距至关重要。