Reassessing vascular endothelial growth factor (VEGF) in anti-angiogenic cancer therapy

• Published in: Cancer treatment and research communications 2022, Vol.32, p.100620-100620, Article 100620
• Main Authors: Elebiyo, Tobiloba C., Rotimi, Damilare, Evbuomwan, Ikponmwosa O., Maimako, Rotdelmwa Filibus, Iyobhebhe, Matthew, Ojo, Oluwafemi Adeleke, Oluba, Olarewaju M., Adeyemi, Oluyomi S.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Anti-angiogenic therapy; Cancer; Tumour blood vessels; Vascular endothelial growth factor (VEGF); Vascular normalization therapy
• ISSN: 2468-2942; 2468-2942
• DOI: 10.1016/j.ctarc.2022.100620

•The role of tumor angiogenesis in tumor growth, metastasis, and drug resistance.•VEGF, VEGFRs, and their inhibitors could glean newer options such as vascular normalization, to enhance anti-angiogenic cancer therapy.•The vascular normalization therapy could be a promising strategy in combating cancer. 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.