血管形成是肿瘤细胞生长和扩散到远处部位的基础。因此,血管生成,新血管从现有血管中发芽,是癌症的特征。1971年,犹大·福克曼(JudahFolkman)假设肿瘤生长依赖于血管生成,并且通过切断血液供应,肿瘤性病变可能会饿死缓解。数十年的研究致力于了解血管内皮生长因子(VEGF)在肿瘤血管生成中的作用,并且它已被确定为在肿瘤块中经常过表达的显著的促血管生成因子。今天,抗VEGF药物如舒尼替尼,索拉非尼,阿西替尼,Tanibirumab,和Ramucirumab已被批准用于治疗晚期和转移性癌症。然而,抗血管生成治疗比原先想象的要复杂。这种治疗选择的失败要求重新评估VEGF作为抗血管生成癌症治疗中的主要靶标。重新评估的呼吁基于两个理由:第一,肿瘤血管异常,杂乱无章,和渗漏;这不仅阻止最佳药物递送,而且还促进缺氧和转移;其次,肿瘤生长或再生长可能是血管依赖性的,而不是血管生成依赖性的,因为肿瘤细胞可以通过非血管生成机制获得血管。因此,对VEGF的严格评估,VEGFR,他们的抑制剂可以收集新的选择,例如将抗VEGF药物重新用作血管正常化剂,以增强免疫检查点抑制剂的药物递送.
Vascularization is fundamental to the growth and spread of tumor cells to distant sites. As a consequence, angiogenesis, the sprouting of new blood vessels from existing ones, is a characteristic trait of cancer. In 1971, Judah Folkman postulated that tumour growth is angiogenesis dependent and that by cutting off blood supply, a neoplastic lesion could be potentially starved into remission. Decades of research have been devoted to understanding the role that vascular endothelial growth factor (VEGF) plays in tumor angiogenesis, and it has been identified as a significant pro-angiogenic factor that is frequently overexpressed within a tumor mass. Today, anti-VEGF drugs such as Sunitinib, Sorafenib, Axitinib, Tanibirumab, and Ramucirumab have been approved for the treatment of advanced and metastatic cancers. However, anti-angiogenic therapy has turned out to be more complex than originally thought. The failure of this therapeutic option calls for a reevaluation of VEGF as the major target in anti-angiogenic cancer therapy. The call for reassessment is based on two rationales: first, tumour blood vessels are abnormal, disorganized, and leaky; this not only prevents optimal drug delivery but it also promotes hypoxia and metastasis; secondly, tumour growth or regrowth might be blood vessel dependent and not angiogenesis dependent as tumour cells can acquire blood vessels via non-angiogenic mechanisms. Therefore, a critical assessment of VEGF, VEGFRs, and their inhibitors could glean newer options such as repurposing anti-VEGF drugs as vascular normalizing agents to enhance drug delivery of immune checkpoint inhibitors.