REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1623859
This article is part of the Research TopicExploring key pathways in the progression of gastrointestinal diseases based on metabolic reprogramming and developing drugs targeting metabolismView all 3 articles
Endostatin-Based Anti-Angiogenic Therapy and Immune Modulation: Mechanisms and Synergistic Potential in Cancer Treatment
Provisionally accepted
- 1Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, China
- 2Department of Psychology, College of Liberal Arts, Wenzhou-Kean University, Wenzhou, China
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Cancer remains a critical global health challenge, driven by tumor angiogenesis and immune evasion. Endostatin, a collagen XVIII-derived fragment, uniquely suppresses angiogenesis and reprograms the immunosuppressive tumor microenvironment (TME), positioning it as a dual-targeting therapeutic. Despite clinical advancements with recombinant human endostatin (rhEs), challenges such as transient efficacy and delivery limitations persist.Emerging strategies integrating nanotechnology, combination therapies, and immunomodulation (e.g., TAM reprogramming, immune checkpoint synergy) aim to amplify its therapeutic potential.This review synthesizes current knowledge on endostatin's mechanisms in angiogenesis inhibition and immune modulation. It further evaluates its clinical efficacy across solid tumors and explores innovative strategies to overcome translational barriers. By dissecting technological advancements, controversies, and synergistic opportunities with radiotherapy, chemotherapy, and immunotherapy, we aim to chart a roadmap for harnessing endostatin's full potential in redefining precision cancer therapeutics. Key word: Endostatin; angiogenesis; immune modulation; peptide derivatives; drug delivery 2 Endostatin in Anti-Angiogenesis Mechanisms Therapies and BeyondEndostatin is a potent inhibitor of angiogenesis, and its mechanisms of action have been the subject of extensive research. One study demonstrated that endostatin -expressing endometrial mesenchymal stem cells (EMSCs -Endo) inhibited angiogenesis in endometriosis through the miRNA -21 -5p/TIMP3/PI3K/Akt/mTOR pathway [1] . In this study, treatment with EMSCs -Endo led to a reduction in the angiogenic capacity of human umbilical vein endothelial cells (HUVECs) in vitro. Specifically, the miRNA -21 -5p level and the levels of p -PI3K, p -mTOR, and p -Akt in HUVECs and mouse endometriotic lesions significantly decreased, while TIMP3 expression significantly increased, as shown in Figure 1.
Keywords: endostatin, Angiogenesis, Immune Modulation, Peptide derivatives, Drug delivery
Received: 06 May 2025; Accepted: 29 May 2025.
Copyright: © 2025 Sun, Ren, Zhao, He, Wang and Ren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
YaXuan Wang, Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, China
Minghua Ren, Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.