Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy

IF 5.8 3区化学 Q1 CHEMISTRY, MEDICINAL

Natural Products and Bioprospecting Pub Date : 2026-09-30 DOI:10.1007/s13659-026-00641-z

Yan-Cai Liu, Yan-Ran Yang, Jiang-Long Wang, Hao-Yang Yu, Min Shao, He-Feng Zhou

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Abstract

The development and drug resistance of breast cancer are closely associated with the heterogeneity of the tumor microenvironment (TME). Immunosuppressive cells, activated matrix components, abnormal vascular networks, and metabolic reprogramming within the TME collectively create a niche that promotes tumor survival. Despite the clinical adoption of emerging therapies such as immune checkpoint inhibitors, overall response rates remain constrained by the suppressive characteristics of the TME. Natural products, with their multi-component, multi-targeted, and low-toxicity advantages, demonstrate significant potential in reshaping the TME. This systematic review summarizes recent advances in natural products regulating the breast cancer TME. We highlight the molecular mechanisms by which natural products reverse immunosuppression, normalize tumor vasculature, inhibit stromal fibrosis, and correct metabolic dysregulation. Additionally, synergistic strategies combining natural products with chemotherapy and immunotherapy are explored, particularly how nanotechnology-based delivery systems overcome pharmacokinetic barriers. Finally, we critically analyze translational challenges in this field and outline future research directions.

Graphical abstract

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靶向肿瘤微环境：天然产物在乳腺癌治疗中的新策略

乳腺癌的发展和耐药与肿瘤微环境（tumor microenvironment， TME）的异质性密切相关。免疫抑制细胞、活化的基质成分、异常血管网络和TME内的代谢重编程共同创造了一个促进肿瘤生存的生态位。尽管临床采用了免疫检查点抑制剂等新兴疗法，但总体缓解率仍然受到TME抑制特性的限制。天然产物以其多组分、多靶点和低毒性的优势，在重塑TME方面显示出巨大的潜力。本文系统综述了调节乳腺癌TME的天然产物的最新进展。我们强调天然产物逆转免疫抑制、使肿瘤血管系统正常化、抑制间质纤维化和纠正代谢失调的分子机制。此外，将天然产物与化疗和免疫疗法相结合的协同策略也被探索，特别是基于纳米技术的递送系统如何克服药代动力学障碍。最后，我们批判性地分析了该领域的翻译挑战，并概述了未来的研究方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Natural Products and Bioprospecting CHEMISTRY, MEDICINAL-

CiteScore

8.30

自引率

2.10%

发文量

审稿时长

13 weeks

期刊介绍： Natural Products and Bioprospecting serves as an international forum for essential research on natural products and focuses on, but is not limited to, the following aspects: Natural products: isolation and structure elucidation Natural products: synthesis Biological evaluation of biologically active natural products Bioorganic and medicinal chemistry Biosynthesis and microbiological transformation Fermentation and plant tissue cultures Bioprospecting of natural products from natural resources All research articles published in this journal have undergone rigorous peer review. In addition to original research articles, Natural Products and Bioprospecting publishes reviews and short communications, aiming to rapidly disseminate the research results of timely interest, and comprehensive reviews of emerging topics in all the areas of natural products. It is also an open access journal, which provides free access to its articles to anyone, anywhere.