Vascular Endothelial Growth Factor (VEGF) inhibitors are medications that target abnormal blood vessel growth. They offer a targeted approach by interfering with specific biological pathways, aiming to improve patient outcomes in various conditions.
The Role of VEGF in the Body
Vascular Endothelial Growth Factor (VEGF) is a signaling protein that plays a central role in angiogenesis, the process by which new blood vessels form from existing ones. This process is normal during embryonic development, wound healing, and after exercise to restore oxygen supply to tissues. VEGF binds to specific receptors on endothelial cells, which line the inside of blood vessels, activating pathways that promote their growth, survival, and permeability.
While VEGF is necessary for healthy bodily functions, its overactivity can contribute to the development and progression of various diseases. An excessive amount of VEGF can lead to the formation of abnormal and leaky blood vessels. This uncontrolled vessel growth can facilitate disease progression, particularly in certain cancers and specific eye disorders.
How VEGF Inhibitors Block Growth
VEGF inhibitors function by targeting and blocking the activity of VEGF or its receptors, thereby preventing the formation of new blood vessels or reducing fluid leakage. This action works by essentially “starving” abnormal cells or tissues, such as tumors, of the blood supply they need to grow. In eye conditions, this mechanism helps reduce fluid leakage and abnormal vessel proliferation, which can otherwise lead to vision loss.
There are different types of VEGF inhibitors, each with a slightly varied approach to blocking the VEGF pathway. Monoclonal antibodies, such as bevacizumab, directly bind to VEGF, stopping it from interacting with its receptors. Other inhibitors are small molecules that block the kinase activity of VEGF receptors, which are enzymes on the cell surface that transmit signals for vessel growth. This prevents the downstream signaling pathways that would otherwise promote endothelial cell proliferation and migration.
Conditions Treated with VEGF Inhibitors
VEGF inhibitors are widely used to treat several medical conditions, primarily focusing on certain cancers and various eye diseases. In oncology, these medications inhibit tumor growth and metastasis by cutting off the blood supply tumors rely on for nutrients and oxygen. They are approved for treating a range of cancers, often in combination with chemotherapy or other targeted therapies to enhance effectiveness:
Metastatic colorectal cancer
Non-small cell lung cancer
Kidney cancer (renal cell carcinoma)
Glioblastoma
Certain types of thyroid cancer
Ovarian cancer
Liver cancers
In ophthalmology, VEGF inhibitors have transformed the management of conditions characterized by abnormal blood vessel growth or leakage in the eye. They are commonly used for wet age-related macular degeneration (AMD), where abnormal blood vessels grow under the retina and leak fluid or blood, causing vision loss. These drugs also treat diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR), complications of diabetes involving abnormal vessel growth and fluid accumulation in the retina. Additionally, they are used for macular edema secondary to retinal vein occlusion (RVO), another condition involving fluid leakage from damaged blood vessels. For eye conditions, these inhibitors are typically administered through intravitreal injections directly into the eye to maximize their local effect.
Understanding Potential Side Effects
Patients receiving VEGF inhibitors may experience various side effects, which can vary depending on the specific medication and individual patient factors. Common systemic side effects include high blood pressure (hypertension) and protein in the urine (proteinuria). Other frequently observed side effects are fatigue and gastrointestinal issues such as diarrhea, nausea, vomiting, and loss of appetite. Hand-foot syndrome, characterized by redness, tenderness, and blistering on the palms and soles, is also a common skin toxicity.
There is also an increased risk of bleeding, bruising, or blood clots. For ocular injections, eye-specific side effects can include eye pain or discomfort, blurred vision, or changes in vision, which are often mild and temporary. More severe, though less common, ocular complications can involve increased intraocular pressure, endophthalmitis, or retinal detachment. Medical professionals carefully monitor patients for these potential side effects throughout the treatment period.