Ganss Ruth
Vascular Biology and Stromal Targeting, Harry Perkins Institute of Medical Research, The University of Western Australia, Centre for Medical Research, Nedlands, Western Australia, Australia.
Vasc Biol. 2020 Jan 14;2(1):R35-R43. doi: 10.1530/VB-19-0032. eCollection 2020.
Tumour growth critically depends on a supportive microenvironment, including the tumour vasculature. Tumour blood vessels are structurally abnormal and functionally anergic which limits drug access and immune responses in solid cancers. Thus, tumour vasculature has been considered an attractive therapeutic target for decades. However, with time, anti-angiogenic therapy has evolved from destruction to structural and functional rehabilitation as understanding of tumour vascular biology became more refined. Vessel remodelling or normalisation strategies which alleviate hypoxia are now coming of age having been shown to have profound effects on the tumour microenvironment. This includes improved tumour perfusion, release from immune suppression and lower metastasis rates. Nevertheless, clinical translation has been slow due to challenges such as the transient nature of current normalisation strategies, limited monitoring and the heterogeneity of primary and/or metastatic tumour environments, calling for more tailored approaches to vascular remodelling. Despite these setbacks, harnessing vascular plasticity provides unique opportunities for anti-cancer combination therapies in particular anti-angiogenic immunotherapy which are yet to reach their full potential.
肿瘤生长严重依赖于包括肿瘤血管系统在内的支持性微环境。肿瘤血管在结构上异常且功能上无反应，这限制了实体癌中药物的进入和免疫反应。因此，几十年来，肿瘤血管系统一直被视为一个有吸引力的治疗靶点。然而，随着时间的推移，随着对肿瘤血管生物学的理解更加精细，抗血管生成治疗已从破坏发展到结构和功能的恢复。缓解缺氧的血管重塑或正常化策略现已成熟，已被证明对肿瘤微环境有深远影响。这包括改善肿瘤灌注、解除免疫抑制和降低转移率。然而，由于当前正常化策略的短暂性、监测有限以及原发性和/或转移性肿瘤环境的异质性等挑战，临床转化一直很缓慢，这就需要更具针对性的血管重塑方法。尽管存在这些挫折，但利用血管可塑性为抗癌联合疗法，特别是抗血管生成免疫疗法提供了独特的机会，而这些疗法尚未发挥其全部潜力。
