Vascular Endothelial Growth Factor, or VEGF, is a protein naturally produced by the body. It plays a part in forming new blood vessels, a process called angiogenesis. This process is necessary for normal development, such as during embryonic growth or for healing after an injury. While this function is beneficial, it can also contribute to the progression of certain diseases when it becomes unregulated.
Medical science has developed a class of drugs designed to target and control the activity of VEGF. These therapies intervene in the signaling process that drives abnormal blood vessel formation. By doing so, they can help manage conditions where excessive angiogenesis is a contributing factor. The goal of these treatments is to restore balance to this process.
The Role of VEGF in Disease
The normal functions of VEGF, such as restoring oxygen supply to tissues, can be exploited by certain diseases. In cancer, many solid tumors harness angiogenesis to ensure their survival and growth. These tumors release large quantities of VEGF, which stimulates the formation of new blood vessels that feed them. This blood supply provides the oxygen and nutrients for the tumor to expand and can facilitate the spread of cancer cells to other parts of the body, a process known as metastasis.
A similar situation occurs in specific diseases of the eye. In conditions like the wet form of age-related macular degeneration (AMD), the body produces an excess of VEGF in the retina. This leads to the growth of new, structurally abnormal blood vessels that are prone to leaking fluid and blood into the macula. The macula is the part of the retina responsible for sharp, central vision, and this leakage can damage retinal cells and lead to severe vision loss.
How VEGF Inhibitors Work
VEGF inhibitors are drugs designed to interrupt the signaling process of the VEGF protein, blocking it from stimulating new blood vessel growth. The most direct mechanism involves the inhibitor drug binding to the VEGF protein itself. This action neutralizes the VEGF protein and prevents it from attaching to its receptors on the surface of endothelial cells, which line blood vessels.
This process can be compared to a key being prevented from entering a lock. The VEGF protein is the key, and the VEGF receptor on the cell is the lock. When the inhibitor binds to the key, it can no longer fit into the lock to send the signal for cells to form new vessels. Halting this initial interaction stops the entire cascade of internal cell signals that leads to angiogenesis.
There are two main categories of VEGF inhibitors. The first type is monoclonal antibodies, which are large protein-based molecules engineered to bind to VEGF proteins circulating in the bloodstream or eye fluid. The second type is small-molecule tyrosine kinase inhibitors. These drugs are small enough to pass through the cell membrane and work from inside the cell, where they block the VEGF receptor’s enzyme activity, preventing the signal from being transmitted.
Conditions Treated with VEGF Inhibitors
VEGF inhibitors are applied to two main categories of medical conditions: cancers and eye diseases. In oncology, these drugs slow the growth of tumors that rely on angiogenesis. Bevacizumab is a monoclonal antibody for treating several types of cancer, including:
- Metastatic colorectal cancer
- Non-small cell lung cancer
- Kidney cancer
- Glioblastoma, an aggressive type of brain tumor
These treatments are administered through intravenous (IV) infusion, allowing the drug to circulate systemically.
In ophthalmology, VEGF inhibitors are a treatment for conditions caused by abnormal blood vessel growth in the retina. These include wet age-related macular degeneration (AMD), diabetic retinopathy, and macular edema (retinal swelling). For these conditions, drugs such as ranibizumab and aflibercept are administered directly into the eye via intravitreal injection. This local delivery method concentrates the medication where it is needed, minimizing its exposure to the rest of the body.
Common Side Effects and Management
Because VEGF helps maintain normal blood vessel function, blocking its activity can lead to side effects. The type and severity of these effects depend on how the drug is administered. For systemic treatments used in cancer therapy, where the drug circulates throughout the bloodstream, side effects are more widespread. Patients may experience an increase in blood pressure, as VEGF signaling helps regulate it.
Other side effects of systemic VEGF inhibitors include an increased risk of bleeding, complications with wound healing, and proteinuria (excess protein in the urine). These effects occur because the drug impacts blood vessels throughout the body. Healthcare providers monitor patients for these issues, managing blood pressure with medication and adjusting treatment schedules around surgeries to allow for proper healing.
For local treatments, such as injections into the eye, side effects are confined to the eye itself. Patients might experience temporary eye pain, floaters, or an increase in intraocular pressure following the injection. There is also a small risk of more serious complications, including inflammation inside the eye, retinal detachment, or endophthalmitis, a severe infection. Ophthalmologists monitor patients closely after each injection to manage these potential issues.