Efforts to develop anti-cancer therapies have largely focused on targeting the epithelial compartment, despite the presence of non-neoplastic stromal components that substantially contribute to the progression of the tumor. Indeed, cancer cell survival, growth, migration and even dormancy are influenced by the surrounding tumor microenvironment (TME). Within the TME, cancer-associated fibroblasts (CAFs) have been shown to play several roles in the development of a tumor. They secrete growth factors, inflammatory ligands and extracellular matrix proteins that promote cancer cell proliferation, therapy resistance and immune exclusion. However, recent work indicates that CAFs may also restrain tumor progression in some circumstances. In this review, we summarize the body of work on CAFs, with a particular focus on the most recent discoveries about fibroblast heterogeneity, plasticity and functions. We also highlight the commonalities of fibroblasts present across different cancer types, and in normal and inflammatory states. Finally, we present the latest advances regarding therapeutic strategies targeting CAFs that are undergoing pre-clinical and clinical evaluation.

中文翻译：

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癌症相关成纤维细胞的多样性和生物学。


尽管存在显着促进肿瘤进展的非肿瘤性基质成分，但开发抗癌疗法的努力主要集中在针对上皮区室。事实上，癌细胞的存活、生长、迁移甚至休眠都受到周围肿瘤微环境（TME）的影响。在 TME 中，癌症相关成纤维细胞 (CAF) 已被证明在肿瘤的发展中发挥多种作用。它们分泌生长因子、炎症配体和细胞外基质蛋白，促进癌细胞增殖、治疗抵抗和免疫排斥。然而，最近的研究表明，CAF 在某些情况下也可能抑制肿瘤进展。在这篇综述中，我们总结了 CAF 的工作主体，特别关注有关成纤维细胞异质性、可塑性和功能的最新发现。我们还强调了不同癌症类型以及正常和炎症状态下成纤维细胞的共性。最后，我们介绍了针对 CAF 的治疗策略的最新进展，这些策略正在进行临床前和临床评估。