Azimi Mohammadreza, Manavi Mahdokht Sadat, Afshinpour Maral, Khorram Roya, Vafadar Reza, Rezaei-Tazangi Fatemeh, Arabzadeh Danyal, Arabzadeh Sattar, Ebrahimi Nasim, Aref Amir Reza
Department of Biochemistry, Medical Faculty, Saveh Branch, Islamic Azad University, Saveh, Iran.
Otolaryngology Department, Tehran University of Medical Science, Tehran, Iran.
Clin Transl Oncol. 2025 Apr;27(4):1406-1425. doi: 10.1007/s12094-024-03667-2. Epub 2024 Sep 18.
Targeting tumor angiogenesis, the formation of new blood vessels supporting cancer growth and spread, has been an intense focus for therapy development. However, benefits from anti-angiogenic drugs like bevacizumab have been limited by resistance stemming from activation of compensatory pathways. Recent immunotherapy advances have sparked interest in novel immunologic approaches that can induce more durable vascular pruning and overcome limitations of existing angiogenesis inhibitors. This review comprehensively examines these emerging strategies, including modulating tumor-associated macrophages, therapeutic cancer vaccines, engineered nanobodies and T cells, anti-angiogenic cytokines/chemokines, and immunomodulatory drugs like thalidomide analogs. For each approach, the molecular mechanisms, preclinical/clinical data, and potential advantages over conventional drugs are discussed. Innovative therapeutic platforms like nanoparticle delivery systems are explored. Moreover, the importance of combining agents with distinct mechanisms to prevent resistance is evaluated. As tumors hijack angiogenesis for growth, harnessing the immune system's specificity to disrupt this process represents a promising anti-cancer strategy covered by this review.
靶向肿瘤血管生成,即支持癌症生长和扩散的新血管形成,一直是治疗开发的重点。然而,像贝伐单抗这样的抗血管生成药物的疗效受到补偿途径激活所产生的耐药性的限制。最近免疫疗法的进展引发了人们对新型免疫方法的兴趣,这些方法可以诱导更持久的血管修剪,并克服现有血管生成抑制剂的局限性。这篇综述全面研究了这些新兴策略,包括调节肿瘤相关巨噬细胞、治疗性癌症疫苗、工程化纳米抗体和T细胞、抗血管生成细胞因子/趋化因子以及沙利度胺类似物等免疫调节药物。对于每种方法,都讨论了其分子机制、临床前/临床数据以及相对于传统药物的潜在优势。还探讨了纳米颗粒递送系统等创新治疗平台。此外,评估了联合使用具有不同机制的药物以预防耐药性的重要性。由于肿瘤利用血管生成来生长,利用免疫系统的特异性来破坏这一过程代表了一种有前景的抗癌策略,本综述对此进行了阐述。