靶向"土壤":乳腺癌治疗的下一个出口

Targeting the"soil":the next frontier in breast cancer treatment

乳腺癌已经成为全球女性发病率最高的癌症,三阴性乳腺癌(TNBC)是乳腺癌中最具有侵袭性的亚型,并且缺乏特定的靶点和靶向治疗。TNBC的肿瘤微环境(TME)与增殖、凋亡抑制、侵袭迁移、血管生成、免疫逃逸和治疗抵抗有关。TME的成分包括转化的细胞外基质(ECM)、可溶性因子、免疫抑制细胞、重编程的肿瘤相关成纤维细胞(CAFs)以及特殊的理化性质共同阻碍抗肿瘤反应并促进TNBC的进展和转移。因此TME可能成为TNBC的治疗靶点。本综述介绍了癌细胞"种子"赖以生存的TME"土壤"的特征,靶向TME的方法,分析了靶向编辑TME中的T细胞、肿瘤相关巨噬细胞(TAMs)、树突状细胞(DC)、CAFs以及理化性质进行抗肿瘤治疗的可行性及其最新进展,最后讨论了当前的挑战和未来的影响。由于TME与TNBC的特征密切相关,了解其不同成分的作用可以提高TNBC患者的临床获益。

Breast cancer has become the most prevalent cancer among women globally.Triple-negative breast cancer(TNBC),the most invasive subtype of breast cancer,lacks specific targets and targeted therapies.The tumor microenvironment(TME)of TNBC is intricately connected with proliferation,apoptosis inhibition,invasion,migration,angiogenesis,immune escape,and therapy resistance.Components of the TME,including transformed extracellular matrix(ECM),soluble factors,immunosuppressive cells,reprogrammed cancer-associated fibroblasts(CAFs),and unique physicochemical properties,collectively impede anti-tumor responses and facilitate the progression and metastasis of TNBC.Hence,the TME is a potential therapeutic target for TNBC.This review delineates the characteristics of the TME"soil"necessary for the sustenance of cancer cell"seeds",the methods of targeting the TME,and analyzes the feasibility and recent advancements in anti-tumor treatments targeting T cells,tumor-associated macrophages(TAMs),dendritic cells(DCs),CAFs,and the physicochemical properties within the TME.Finally,it discusses current challenges and future implications.Understanding the diverse roles of the TME components in relation to TNBC is pivotal for enhancing clinical benefits in TNBC patients.