Department of Biochemistry, Landmark University, Omu-Aran, Nigeria.
Department of Microbiology, Landmark University, Omu-Aran, Nigeria.
Cancer Treat Res Commun. 2022;32:100620. doi: 10.1016/j.ctarc.2022.100620. Epub 2022 Aug 6.
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.
血管生成对于肿瘤细胞向远处转移和生长至关重要。因此，血管生成，即新血管从现有血管中萌发，是癌症的一个特征。1971 年， Judah Folkman 假设肿瘤生长依赖于血管生成，通过切断血液供应，可以使肿瘤病变潜在地饿死进入缓解状态。几十年来，人们一直在研究血管内皮生长因子（VEGF）在肿瘤血管生成中的作用，并已确定其为一种重要的促血管生成因子，在肿瘤组织中经常过度表达。如今，已有多种抗 VEGF 药物（如舒尼替尼、索拉非尼、阿昔替尼、坦西布单抗和雷莫芦单抗）获批用于治疗晚期和转移性癌症。然而，抗血管生成疗法比最初想象的要复杂得多。这种治疗选择的失败呼吁重新评估 VEGF 作为抗血管生成癌症治疗的主要靶点。重新评估的呼吁基于两个理由：首先，肿瘤血管是异常的、紊乱的和渗漏的；这不仅阻止了最佳的药物输送，而且还促进了缺氧和转移；其次，肿瘤生长或复发可能依赖于血管而不是血管生成，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、VEGFR 及其抑制剂进行批判性评估，可以获得新的选择，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输送。
