What is Anti-VEGF Therapy?
Anti-VEGF therapy consists of drugs that block vascular endothelial growth factor (VEGF), a protein that stimulates abnormal blood vessel growth in tumors and various eye diseases, thereby inhibiting angiogenesis and reducing vascular permeability. 1
Mechanism of Action
Anti-VEGF agents work by targeting the VEGF signaling pathway, which is essential for both normal and pathological blood vessel formation. VEGF normally binds to receptors on endothelial cells, activating intracellular pathways that promote:
- Endothelial cell proliferation, migration, and survival
- New blood vessel formation (angiogenesis)
- Increased vascular permeability
- Recruitment of vascular precursor cells 1, 2
By blocking VEGF from interacting with its receptors, these therapies prevent new vessel formation and cause regression of newly formed microvessels, while normalizing abnormal tumor or retinal vasculature. 1
Types of Anti-VEGF Agents
There are two main categories of VEGF inhibitors:
Monoclonal Antibodies (Target VEGF Ligand)
- Bevacizumab (Avastin): A humanized monoclonal antibody that binds all isoforms of VEGF 1, 3
- Ranibizumab (Lucentis): FDA-approved for intravitreal use in eye diseases 3
- Aflibercept: Approved for neovascular AMD and other retinal conditions 3
Tyrosine Kinase Inhibitors (Target VEGF Receptors)
- Sunitinib, sorafenib, cediranib, nintedanib, pazopanib
- These block VEGF receptor functions directly 1
Clinical Applications
Oncology
Anti-VEGF therapy is used to treat various cancers by:
- Disrupting tumor blood supply
- Limiting tumor growth and metastasis
- Normalizing tumor vasculature to improve oxygenation and enhance other treatments 1, 4
Bevacizumab has FDA approval for metastatic colorectal, breast, and non-small cell lung cancer 3. In ovarian and cervical cancers, it may prolong survival when combined with chemotherapy 1.
Ophthalmology
Anti-VEGF therapy has revolutionized treatment of retinal diseases and is now the standard of care for:
- Neovascular age-related macular degeneration (AMD): Most common indication, with proven vision improvement 3, 5
- Diabetic macular edema and proliferative diabetic retinopathy 6, 7
- Retinal vein occlusion 6
- Retinopathy of prematurity 7
These agents are administered via intravitreal injection at regular intervals 6.
Important Side Effects and Considerations
Cardiovascular Effects
Hypertension is a recognized class effect of all anti-angiogenic therapies, including bevacizumab. 1 The mechanism involves:
- Decreased nitric oxide production (normally VEGF stimulates NO, which causes vasodilation)
- Deficiency in vasodilators like prostacyclin
- Increased vasoconstrictive factors (endothelin-1)
- Reduction in capillary bed density (rarefaction)
- Increased peripheral vascular resistance 1
Ocular Complications (Intravitreal Use)
- Endophthalmitis (≤1.0% cumulative risk over 1 year) 3
- Retinal detachment or tear
- Noninfectious inflammation
- Increased intraocular pressure 3
Systemic Risks
All anti-VEGF treatments carry theoretical risks for:
- Arterial thromboembolic events
- Venous thrombosis
- Gastrointestinal disorders including hemorrhage 3
The CATT study showed bevacizumab had a higher rate of serious systemic events (24%) compared to ranibizumab (19%, P=0.04) at 1 year, though differences in death or specific thrombotic events were not statistically significant 3.
Clinical Pitfalls
- Pregnancy and lactation: Risks have not been studied; use with extreme caution 3
- Radiation therapy combinations: When combined with radiotherapy, VEGF(R) inhibitors can increase mucosal/gastrointestinal toxicity, hemorrhage risk, and fistula formation 4
- Long-term efficacy: Vision gains in AMD may not be maintained beyond 2 years without continued treatment 3
- Treatment burden: Requires frequent clinic visits and repeated injections for ophthalmologic indications 7