Drug resistance mechanism of anti-angiogenesis therapy in tumor

Yi Chuan. 2024 Nov;46(11):911-919. doi: 10.16288/j.yczz.24-110.

Abstract

Angiogenesis refers to the process of forming a new network of blood vessels from existing ones through the migration, proliferation, and differentiation of endothelial cells. This process is crucial for the growth and spread of solid tumors, particularly once the tumor volume exceeds 2 mm3, as the newly formed vascular network provides essential oxygen, nutrients, and growth factors to the tumor. Anti-angiogenesis therapy has become one of the commonly used targeted treatments for cancer in clinical practice. Bevacizumab, the first anti-angiogenesis drug, has been widely applied in the treatment of various solid tumors. However, due to acquired resistance, its efficacy is typically sustained for only 1 to 2 years. Despite the relative genomic stability of endothelial cells, which makes resistance less likely, various types of resistance phenomena have been observed in clinical practice, indicating that resistance to anti-angiogenic therapy remains a challenging research area. This review focuses on the latest advances in the mechanisms of resistance to anti-angiogenic therapy in tumors and explores new prospects for anti-tumor angiogenesis treatment, in order to provide strong theoretical support and guidance for clinical practice.

血管生成指的是通过内皮细胞的迁移、增殖和分化,从现有血管网络中形成新的血管网络的过程。这一过程对于实体肿瘤的生长和扩散至关重要,尤其是在肿瘤体积超过2 mm3之后,新生的血管网络为肿瘤提供了至关重要的氧气、营养及生长因子。抗血管生成已经成为临床常用靶向治疗肿瘤的方案之一。首个抗血管生成药物贝伐单抗已广泛应用于多种实体肿瘤治疗,但由于获得性耐药现象,疗效仅能维持1~2年。即使血管内皮细胞的基因组相对稳定,不易产生耐药性,但临床实践中仍观察到多种类型的耐药现象,这表明抗血管生成治疗的耐药问题仍然是一个具有挑战性的研究领域。本文主要综述了肿瘤抗血管生成治疗耐药机制的最新进展,并探讨了抗肿瘤血管生成治疗的新前景,以期为临床实践提供有力的理论支持和指导。.

Keywords: anti-angiogenic drugs; intussusceptive angiogenesis; tumor drug resistance; vasculogenic mimicry; vessel co-option.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors* / pharmacology
  • Angiogenesis Inhibitors* / therapeutic use
  • Animals
  • Drug Resistance, Neoplasm*
  • Humans
  • Neoplasms* / blood supply
  • Neoplasms* / drug therapy
  • Neovascularization, Pathologic* / drug therapy

Substances

  • Angiogenesis Inhibitors