VEGFA-165 dimer binds VEGFA inhibitors

Stable Identifier
Reaction [binding]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
Orthologous Events
Cite Us!