靶向肿瘤相关成纤维细胞的肿瘤治疗研究进展

肿瘤是威胁人类生命健康的主要疾病之一。肿瘤细胞和肿瘤微环境(tumor microenvironment,TME)的相互作用在肿瘤发生、发展、转移和治疗过程中发挥关键作用。肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)是TME的重要组成部分,是一类具极强增殖、迁移、分泌与合成能力的激活态成纤维细胞。研究发现,CAFs可直接与肿瘤细胞相互作用,提高肿瘤细胞干性,促进肿瘤的侵袭和转移;还可分泌多种细胞因子、趋化因子和生长因子等介导与肿瘤细胞存活、免疫调节相关的信号通路,间接发挥促肿瘤作用。因此,靶向CAFs成为开发新的肿瘤治疗药物和策略的研究热点。该文概述了CAFs的来源、CAFs与TME中肿瘤细胞和基质细胞之间的相互作用、靶向CAFs的肿瘤治疗策略、CAFs作为肿瘤预后生物标志物的可能性及其存在的问题和挑战,为以CAFs为靶点的新型肿瘤治疗策略的应用提供依据。

Research progress of tumor therapy targeting cancer-associated fibroblasts

Tumor is one of the main diseases that threaten the health of human.The interaction between tumor cells and tumor microenvironment(TME)plays a key role in the occurrence,development,metastasis and treatment of tumors.Cancer-associated fibroblasts(CAFs),an important component of TME,are activated fibroblasts with strong capabilities for proliferation,migration,as well as secretion and synthesis.It has been found that CAFs can directly interact with tumor cells,improve the stemness of tumor cells,and promote tumor invasion and metastasis.CAFs can also indirectly promote tumor development by secreting cytokine,chemokines and growth factor to mediate the signaling pathways related to tumor survival and immune regulation.Therefore,the development of novel tumor therapeutic drugs and strategies targeting CAFs has become research hotspots.This review summarized the origin of CAFs,the interaction of CAFs with tumor cells and stromal cells in TME,the potent tumor therapeutic strategies targeting CAFs,and the possibilities of CAFs as cancer prognostic biomarkers as well as the existing challenges,which would provide theoretical basis for CAFs-targeting strategies for tumor therapy.