Reactome | VEGFA-165 dimer binds VEGFA inhibitors

VEGFA-165 dimer binds VEGFA inhibitors

Stable Identifier

R-HSA-9679477

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region

ReviewStatus

5/5

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In normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angiogenesis). In tumor progression, activation of VEGF pathways promotes tumor vascularization, facilitating tumor growth and metastasis. Abnormal VEGF function is also associated with inflammatory diseases including atherosclerosis, and hyperthyroidism. Inhibition of this process may provide clinical benefits to patients suffering from cancer, diabetic macular edema (DME) and age-related macular degeneration (AMD). VEGFA inhibitors are therapeutic options for these diseases (Melincovici et al. 2018, Aguilar-Cazares et al. 2019, Kim et al. 2019).

Aflibercept is a recombinant protein which is indicated for DME, AMD and part of a combined treatment for metastatic colorectal cancer (Chu 2009, Tang & Moore 2013).

Abicipar Pegol (MP0112) is an investigational compound that has been used in trials studying the treatment of DME and AMD (Campochiaro et al. 2013).

Brolucizumab (RTH258, ESBA1008,4) is a monoclonal antibody indicated to treat AMD (Yannuzzi et al. 2019).

Pegaptanib is a polynucleotide aptamer used to treat AMD (Gragoudas et al. 2004, Vinores 2006).

Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. It is indicated for the treatment of DME and AMD (Nguyen et al. 2006, Ferrara et al. 2006).

Vanucizumab is an investigational monoclonal antibody that has been used in trials studying the treatment of colorectal cancer and advanced/metastatic solid tumours (Hidalgo et al. 2018, Bendell et al. 2019).

Bevacizumab (Avastin) is a humanized monoclonal IgG antibody, and inhibits angiogenesis by binding and inhibiting VEGFA (Papachristos et al. 2019). Researchers have identified higher VEGF expression in patients with COVID-19, which may contribute to lung pathologies. Bevacizumab is being investigated for the treatment of lung complications associated with severe cases of COVID-19 (Phase 2/3 NCT04275414) (Rosa & Santos 2020).

Literature References

PubMed ID	Title	Journal	Year
17046701	Vascular endothelial growth factor is a critical stimulus for diabetic macular edema Zimmer-Galler, I, Shah, SM, Quinlan, E, Haller, JA, Do, DV, Campochiaro, PA, Tatlipinar, S, Sung, J, Nguyen, QD	Am. J. Ophthalmol.	2006
24179482	Aflibercept in the treatment of patients with metastatic colorectal cancer: latest findings and interpretations Tang, PA, Moore, MJ	Therap Adv Gastroenterol	2013
15625332	Pegaptanib for neovascular age-related macular degeneration Adamis, AP, Guyer, DR, Gragoudas, ES, Cunningham, ET, Feinsod, M	N. Engl. J. Med.	2004
31413539	Brolucizumab: evidence to date in the treatment of neovascular age-related macular degeneration Yannuzzi, NA, Freund, KB	Clin Ophthalmol	2019
29217526	First-in-Human Phase I Study of Single-agent Vanucizumab, A First-in-Class Bispecific Anti-Angiopoietin-2/Anti-VEGF-A Antibody, in Adult Patients with Advanced Solid Tumors Morel, A, Boni, V, Krieter, O, Rossomanno, S, Boetsch, C, Bahleda, R, Lechner, K, Nayak, T, Sablin, MP, Martinez-Garcia, M, Varga, A, Le Tourneau, C, Franjkovic, I, Alt, M, Albanell, J, Stubenrauch, K, Massard, C, Smart, K, Heil, F, Garralda, E, Lahr, A, Taus, A, Hidalgo, M	Clin. Cancer Res.	2018
31752122	VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer Panoilia, E, Kemos, P, Sivolapenko, GB, Kalofonos, H, Patrinos, GP, Papachristos, A, Katsila, T	Int J Mol Sci	2019
17717967	Pegaptanib in the treatment of wet, age-related macular degeneration Vinores, SA	Int J Nanomedicine	2006
17031284	Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration Lowman, H, Shams, N, Ferrara, N, Kim, R, Damico, L	Retina (Philadelphia, Pa.)	2006
23218689	Treatment of diabetic macular edema with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study Brown, DM, Berger, BB, Channa, R, Stumpp, MT, Fiedler, U, Heier, JS, Hepp, J, Campochiaro, PA	Am. J. Ophthalmol.	2013
31570519	The McCAVE Trial: Vanucizumab plus mFOLFOX-6 Versus Bevacizumab plus mFOLFOX-6 in Patients with Previously Untreated Metastatic Colorectal Carcinoma (mCRC) Krieter, O, Samuel, L, Boetsch, C, Plezia, P, López-López, C, Gracián, AC, Hussein, M, Vivas, CS, Lahr, A, Alvarez, R, Cervantes, A, Rossomanno, S, Moons, V, Bennouna, J, Lechner, K, García-Alfonso, P, Sauri, T, Hurwitz, H, Franjkovic, I, Miron, ML, Andel, J, Montagut, C, Bendell, JC, Heil, F, Bessudo, A, van der Westhuizen, A	Oncologist	2019
19236257	Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors Chu, QS	Expert Opin Biol Ther	2009