Angiogenesis is the body’s process for creating new blood vessels from ones that already exist. This function is a normal part of growth and healing, such as in repairing wounds, ensuring tissues receive needed oxygen and nutrients. The body maintains a careful balance of factors that either encourage or inhibit this process. An anti-angiogenic substance or therapy is one that intentionally disrupts this process, slowing or stopping the creation of new blood vessels. This intervention becomes medically relevant when abnormal vessel growth contributes to disease.
The Anti-Angiogenic Mechanism
Certain tissues, especially cancerous tumors, require a dedicated blood supply to grow beyond a very small size. To do this, they release chemical signals that encourage nearby blood vessels to grow toward them. This process provides the tissue with the oxygen and nutrients necessary for expansion. These signals act as a “go” command for the endothelial cells that line blood vessels, prompting them to multiply and form new vascular pathways.
A primary signaling molecule in this process is the Vascular Endothelial Growth Factor (VEGF). It functions as a messenger, instructing blood vessels to sprout and extend. Anti-angiogenic therapies are designed to interrupt this communication by preventing the growth signals from reaching their intended targets on the endothelial cells.
There are two main strategies for achieving this blockade. One approach involves using agents that attach to the VEGF molecules themselves, neutralizing them. A second strategy involves blocking the specific receptors on the surface of the endothelial cells, which prevents the VEGF signal from being received.
Medical Applications
In oncology, anti-angiogenic therapies are used to slow the progression of various solid tumors. Cancers in the colon, lung, kidney, and brain rely on new blood vessels to grow and metastasize, or spread to other parts of the body. By inhibiting angiogenesis, these treatments cut off a tumor’s supply of oxygen and nutrients. This can slow tumor enlargement and is often used alongside other cancer treatments like chemotherapy.
The field of ophthalmology also utilizes these treatments for specific eye conditions. One such condition is wet age-related macular degeneration (AMD), where abnormal blood vessels grow underneath the retina. These new vessels are fragile and can leak blood and fluid, causing damage to the macula and leading to severe vision loss.
Diabetic retinopathy, another condition treated with these therapies, involves abnormal blood vessel growth in the retina as a complication of diabetes. In both conditions, anti-angiogenic drugs are administered directly into the eye. These targeted injections help reduce the growth of these harmful vessels, which can preserve or improve vision.
Types of Anti-Angiogenic Treatments
One class of anti-angiogenic drugs is monoclonal antibodies. These are laboratory-engineered proteins designed to recognize and bind to specific molecular targets. A well-known example is bevacizumab, which is engineered to target the VEGF protein directly. By binding to VEGF, it prevents the growth factor from interacting with its receptors on blood vessel cells.
Another category of treatment is Tyrosine Kinase Inhibitors (TKIs). Unlike monoclonal antibodies that work outside the cell, TKIs are small-molecule drugs that penetrate the cell membrane and work from within. They function by blocking the signaling pathways that are triggered after a growth factor binds to its receptor. Drugs like sunitinib and sorafenib are examples of TKIs that inhibit the activity of VEGF receptors, preventing the cell from receiving the command to grow and divide. These inhibitors often target multiple kinase enzymes, allowing them to disrupt several signaling pathways at once.
Associated Side Effects and Complications
Because angiogenesis is a process for maintaining healthy tissues, therapies designed to inhibit it can cause a range of side effects. Normal bodily functions, such as tissue repair and blood pressure regulation, rely on the controlled growth of new blood vessels, so interfering with this process can lead to unintended consequences.
A common side effect is hypertension, or high blood pressure. The inhibition of VEGF can affect the function of existing blood vessels, leading to constriction and an increase in blood pressure. Another frequent complication is impaired wound healing. Since the formation of new blood vessels is a necessary step in repairing damaged tissue, patients on these therapies may find that cuts and surgical incisions heal more slowly.
More serious complications, though less common, can also occur. These include an increased risk of bleeding or the formation of blood clots, which are tied to the therapy’s impact on endothelial cells and platelets. In rare instances, gastrointestinal perforation—a hole in the stomach or intestines—can happen.