Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Sidney Kimmel Comprehensive Cancer Center, The Skip Viragh Pancreatic Cancer Center for Clinical Research and Care, and The Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Chin Med J (Engl). 2024 Mar 20;137(6):638-650. doi: 10.1097/CM9.0000000000003031. Epub 2024 Feb 29.
Anti-cancer therapies usually focus on tumor cells, but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression, which may be the prognostic factors and potential therapeutic targets. Cancer-associated fibroblasts (CAFs) are the essential component in the tumor environment, exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis, immune systems, and metabolism. Single-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity, and many subtypes have been defined. However, the precise functions of these subtypes need to be studied and validated. Studies of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic targets. Some clinical trials, including phase III trials targeting CAFs, have been performed recently. However, few of these trials have generated promising results, which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown, and in-depth investigations of CAFs should be performed. This review summarizes the research on CAFs, focusing on the heterogeneity of their phenotypes and functions, specific signaling pathways, and the therapeutic strategies involving CAFs. Additionally, we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.
抗癌疗法通常侧重于肿瘤细胞，但肿瘤微环境中的非肿瘤基质成分在肿瘤发生和进展中也起着至关重要的作用，它们可能是预后因素和潜在的治疗靶点。癌相关成纤维细胞（CAFs）是肿瘤微环境中的重要组成部分，其细胞起源和表型具有高度异质性，具有多种功能，影响肿瘤血管生成、免疫系统和代谢。单细胞 RNA 测序和基因工程小鼠模型增加了我们对 CAF 多样性的理解，已经定义了许多亚型。然而，这些亚型的确切功能需要进行研究和验证。对 CAFs 中信号通路和表观遗传变化的研究有助于理解 CAFs 的表型以及肿瘤细胞和 CAFs 之间的串扰，从而提供潜在的治疗靶点。最近已经进行了一些针对 CAFs 的临床试验，包括 III 期临床试验。然而，这些试验中很少有产生有希望的结果，这表明肿瘤微环境中 CAFs 的复杂性在很大程度上尚不清楚，应该对 CAFs 进行深入研究。这篇综述总结了 CAFs 的研究，重点介绍了其表型和功能、特定信号通路以及涉及 CAFs 的治疗策略。此外，我们还简要讨论了 CAF 研究中常用的当前技术，并描述了 CAF 研究的挑战和未来展望。
