Matuszewska Kathy, Pereira Madison, Petrik Duncan, Lawler Jack, Petrik Jim
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Cancers (Basel). 2021 Sep 3;13(17):4444. doi: 10.3390/cancers13174444.
A basic requirement of tumorigenesis is the development of a vascular network to support the metabolic requirements of tumor growth and metastasis. Tumor vascular formation is regulated by a balance between promoters and inhibitors of angiogenesis. Typically, the pro-angiogenic environment created by the tumor is extremely aggressive, resulting in the rapid vessel formation with abnormal, dysfunctional morphology. The altered morphology and function of tumor blood and lymphatic vessels has numerous implications including poor perfusion, tissue hypoxia, and reduced therapy uptake. Targeting tumor angiogenesis as a therapeutic approach has been pursued in a host of different cancers. Although some preclinical success was seen, there has been a general lack of clinical success with traditional anti-angiogenic therapeutics as single agents. Typically, following anti-angiogenic therapy, there is remodeling of the tumor microenvironment and widespread tumor hypoxia, which is associated with development of therapy resistance. A more comprehensive understanding of the biology of tumor angiogenesis and insights into new clinical approaches, including combinations with immunotherapy, are needed to advance vascular targeting as a therapeutic area.
肿瘤发生的一个基本要求是形成血管网络，以支持肿瘤生长和转移的代谢需求。肿瘤血管形成受血管生成促进因子和抑制因子之间平衡的调节。通常，肿瘤产生的促血管生成环境极具侵袭性，导致快速形成形态异常、功能失调的血管。肿瘤血管和淋巴管形态与功能的改变会产生诸多影响，包括灌注不良、组织缺氧和治疗药物摄取减少。将肿瘤血管生成作为一种治疗方法已在多种不同癌症中展开探索。尽管在临床前研究中取得了一些成功，但传统抗血管生成疗法作为单一药物在临床上普遍缺乏成效。通常，抗血管生成治疗后，肿瘤微环境会发生重塑，出现广泛的肿瘤缺氧，这与治疗耐药性的产生有关。需要更全面地了解肿瘤血管生成生物学，并深入洞察新的临床方法，包括与免疫疗法联合使用，以推动血管靶向治疗领域的发展。
