Vascular Endothelial Growth Factor (VEGF) is a natural signaling protein produced by cells throughout the body. Its primary function is to stimulate the formation and maintenance of blood vessels. When the body needs new blood supply, such as during growth or repair, VEGF acts as a molecular messenger to initiate this process. The development of drugs that specifically block the action of this protein has transformed the treatment landscape for several complex diseases. These anti-VEGF medications work by interrupting the abnormal processes driven by an overabundance of this signaling molecule.
The Biological Function of VEGF
The normal role of VEGF is to promote a process called angiogenesis. This function is necessary for life processes, including the healing of wounds and the body’s natural response to a lack of oxygen in tissues. VEGF binds to specific receptors located on the surface of endothelial cells, which form the inner lining of blood vessels. This binding event triggers a cascade of internal signals that tells the cell to multiply, move, and increase the permeability of the vessel wall.
In healthy adults, VEGF activity is tightly controlled and usually low, but certain diseases cause the body to overproduce it. This excessive signaling leads to pathological angiogenesis, resulting in the growth of new blood vessels that are often disorganized, fragile, and prone to leakage. In the eye, these abnormal, leaky vessels can cause swelling and damage the retina, while in cancer, they form a supply network that delivers oxygen and nutrients to rapidly growing tumors. Anti-VEGF therapies are based on the understanding that blocking this overactive signal can halt disease progression.
How Anti-VEGF Drugs Interrupt Disease
Anti-VEGF drugs are designed to physically interfere with the VEGF signaling pathway. This intervention focuses on preventing the VEGF protein from activating its receptors on the endothelial cells. The drugs accomplish this goal through two main strategies: neutralizing the protein itself or blocking the receptor on the cell surface.
The first strategy involves using drugs that act as molecular “traps” or neutralizers for the VEGF protein circulating outside the cell. These drugs, such as monoclonal antibodies, bind directly to the VEGF protein and sequester it. By binding to the protein, they prevent it from attaching to the receptors on the endothelial cell surface, effectively shutting down the signal for new vessel growth and vessel leakage.
The second approach uses small molecule inhibitors that target the receptor on the cell’s surface. These drugs block the internal signaling machinery of the receptor, known as tyrosine kinase activity. Even if the VEGF protein manages to bind to the receptor, the necessary signal is not transmitted inside the cell to initiate vessel proliferation or increased permeability. Whether the protein is trapped or the receptor is blocked, the result is a reduction in pathological blood vessel formation, which helps regress existing abnormal vessels and reduce damaging fluid leakage.
Major Conditions Treated by VEGF Inhibitors
VEGF inhibitors have become standard treatments across two major fields of medicine: ophthalmology and oncology. In the eye, these drugs treat conditions involving abnormal vessel growth and fluid leakage in the macula. Wet Age-Related Macular Degeneration (AMD) is a primary target, where fragile new blood vessels grow beneath the retina, leaking fluid and blood that quickly destroys central vision.
Diabetic Retinopathy and Diabetic Macular Edema are also treated with these medications when high blood sugar levels lead to excess VEGF production. The resulting abnormal vessels and excessive fluid accumulation cause swelling in the retina, leading to impaired vision. The medication is typically administered directly into the vitreous gel of the eye through a precise injection. This localized delivery minimizes systemic exposure while maximizing the therapeutic effect on the retina.
In cancer treatment, anti-VEGF therapy is used to cut off the blood supply to rapidly dividing tumor cells. Tumors must recruit new blood vessels to sustain their aggressive growth, and by inhibiting VEGF, the drugs can slow down this process. This approach is often used in combination with chemotherapy to enhance the effectiveness of treatment. Cancers commonly treated with this class of drug include metastatic colorectal cancer, non-small cell lung cancer, and kidney cancer. By disrupting the tumor’s ability to create a vascular network, VEGF inhibitors help to starve the malignant tissue and inhibit its spread.