Mahaki Hanie, Nobari Sima, Tanzadehpanah Hamid, Babaeizad Ali, Kazemzadeh Gholamhosein, Mehrabzadeh Mohsen, Valipour Arezoo, Yazdinezhad Nader, Manoochehri Hamed, Yang Piao, Sheykhhasan Mohsen
Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Deputy of Health, Iran University of Medical Science, Tehran, Iran.
Biomed Pharmacother. 2025 May;186:118023. doi: 10.1016/j.biopha.2025.118023. Epub 2025 Mar 30.
The tumor microenvironment (TME) plays a pivotal role in cancer progression and metastasis, with vascular endothelial growth factor (VEGF) signaling serving as a key regulator of tumor angiogenesis and immune evasion. VEGF induces abnormal blood vessel formation, promoting tumor growth, immune suppression, and metastasis through epithelialmesenchymal transition (EMT). As a result, VEGF signaling has become a critical therapeutic target in cancer treatment. This review examines the molecular mechanisms driving VEGF-mediated tumor growth and angiogenesis, with a focus on the interaction between tumor and endothelial cells and the dual role of VEGF in fostering vascularization and immune suppression. Current anti-VEGF therapies, including monoclonal antibodies (e.g., bevacizumab) and tyrosine kinase inhibitors (TKIs), have demonstrated efficacy and have received FDA approval for various cancers; however, therapeutic resistance remains a significant challenge. Strategies to overcome resistance, such as novel VEGF inhibitors, vascular normalization approaches, and combination therapies with immune checkpoint inhibitors, have been explored. Additionally, future directions emphasize the need for personalized approaches to improve treatment efficacy and reduce metastasis. A comprehensive understanding of VEGF signaling in the TME may pave the way for more effective cancer therapies.
肿瘤微环境（TME）在癌症进展和转移中起着关键作用，血管内皮生长因子（VEGF）信号传导是肿瘤血管生成和免疫逃逸的关键调节因子。VEGF诱导异常血管形成，通过上皮-间质转化（EMT）促进肿瘤生长、免疫抑制和转移。因此，VEGF信号传导已成为癌症治疗中的关键治疗靶点。本综述探讨了驱动VEGF介导的肿瘤生长和血管生成的分子机制，重点关注肿瘤细胞与内皮细胞之间的相互作用以及VEGF在促进血管生成和免疫抑制中的双重作用。目前的抗VEGF疗法，包括单克隆抗体（如贝伐单抗）和酪氨酸激酶抑制剂（TKIs），已显示出疗效，并已获得FDA批准用于治疗各种癌症；然而，治疗耐药性仍然是一个重大挑战。人们已经探索了克服耐药性的策略，如新型VEGF抑制剂、血管正常化方法以及与免疫检查点抑制剂的联合疗法。此外，未来的方向强调需要个性化方法来提高治疗效果并减少转移。全面了解TME中的VEGF信号传导可能为更有效的癌症治疗铺平道路。
