Background

Angiogenesis is a key and early step in tumorigenesis, and is known as a hallmark of solid tumors and a key promoter of tumor recurrence. Unlike normal tissue vessels, the architecture of the tumor vasculature is abnormal, being leaky, tortuous, fragile and blind-ended. Perivascular cells are either detached or absent, causing reduction of vascular integrity, an increase in vessel immaturity, incoherent perfusion, defective functionality and enhanced tumor dissemination and metastasis. The abnormal tumor vasculature along with the defective tumor vessel functionality finally causes bouts of hypoxia and acidity in the tumor microenvironment (TME), further reinvigorating tumor aggression. Interstitial hypertension or high interstitial fluid pressure (IFP) is an outcome of tumor hyper-permeability. High IFP can be a barrier for either effective delivery of anti-cancer drugs toward the TME or accumulation of drugs within the tumor area, thus promoting tumor resistance to therapy. Some tumors do, however, not undergo angiogenesis but instead undergo vessel co-option or vascular mimicry, thereby adding another layer of complexity to cancer development and therapy.

Conclusions

Combination of anti-angiogenesis therapy with chemotherapy and particularly with immune checkpoint inhibitors (ICIs) is a promising strategy for a number of advanced cancers. Among the various approaches for targeting tumor angiogenesis, vascular normalization is considered as the most desired method, which allows effective penetration of chemotherapeutics into the tumor area, thus being an appropriate adjuvant to other cancer modalities.

中文翻译：

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血管生成是实体瘤的标志——临床观点

背景

血管生成是肿瘤发生的关键和早期步骤，被称为实体瘤的标志和肿瘤复发的关键促进因素。与正常组织血管不同，肿瘤脉管系统的结构是异常的、渗漏的、曲折的、脆弱的和盲端的。血管周围细胞脱落或缺失，导致血管完整性降低、血管不成熟增加、灌注不连贯、功能缺陷和肿瘤扩散和转移增强。异常的肿瘤脉管系统以及有缺陷的肿瘤血管功能最终导致肿瘤微环境 (TME) 出现缺氧和酸性，进一步重振肿瘤侵袭性。间质性高血压或高间质液压力 (IFP) 是肿瘤高渗透性的结果。高 IFP 可能成为抗癌药物有效递送至 TME 或药物在肿瘤区域内积累的障碍，从而促进肿瘤对治疗的抵抗力。然而，一些肿瘤确实不经历血管生成，而是经历血管共同选择或血管模拟，从而为癌症发展和治疗增加了另一层复杂性。

结论

抗血管生成疗法与化学疗法，特别是与免疫检查点抑制剂 (ICI) 的结合是许多晚期癌症的有希望的策略。在靶向肿瘤血管生成的各种方法中，血管正常化被认为是最理想的方法，它允许化学治疗剂有效地渗透到肿瘤区域，因此是其他癌症方式的适当辅助手段。