Angiogenesis is the natural process by which the body forms new blood vessels from existing ones. This intricate biological function is fundamental for numerous physiological processes throughout life, supporting growth, development, and repair within the body. However, this same process can be exploited in disease states, particularly in the context of cancer, where it plays a significant role in tumor progression. Understanding how angiogenesis works in both healthy and diseased conditions is important.
Angiogenesis: The Body’s Natural Blood Vessel Formation
Angiogenesis is a continuous process that begins even before birth and persists throughout an individual’s life. It involves the growth of new capillaries, which are tiny blood vessels, from pre-existing ones. These capillaries are responsible for delivering oxygen and nutrients to tissues and organs, while also removing waste products.
In healthy individuals, angiogenesis is a tightly controlled and regulated process. It activates only when and where new blood vessels are needed, such as during wound healing, tissue repair, or embryonic development. For instance, if a tissue experiences a lack of oxygen (hypoxia), cells in that area will release chemical signals that trigger angiogenesis to restore blood supply.
Endothelial cells, which line the inside of blood vessels, play a central role by proliferating, migrating, and organizing to form these new vascular structures. The balance between signals that promote and inhibit angiogenesis maintains this precise control.
Cancer’s Exploitation of Angiogenesis
Cancer cells manipulate the body’s natural angiogenic mechanisms to fuel their unchecked growth and survival. Tumors, like any other rapidly growing tissue, require a dedicated blood supply for oxygen, nutrients, and waste removal. Without this blood supply, a tumor typically cannot grow beyond a very small size, generally about 1 to 2 millimeters in diameter.
To overcome this limitation, cancer cells “switch on” angiogenesis by secreting various growth factors and signaling molecules. A primary molecule involved in this process is Vascular Endothelial Growth Factor (VEGF). Tumor cells, especially under hypoxic conditions, upregulate the expression of VEGF, which then binds to its receptors on nearby endothelial cells. This binding initiates a signaling cascade within these endothelial cells, promoting their proliferation, migration, and the formation of new blood vessel sprouts.
These newly formed tumor blood vessels are often structurally abnormal and irregularly shaped. This network of new vessels not only provides the tumor with a constant supply of oxygen and nutrients, but also creates pathways for cancer cells to enter the bloodstream. Once in the bloodstream, these cells can travel to distant parts of the body and establish new tumor colonies, a process known as metastasis.
Inhibiting Angiogenesis as a Cancer Treatment Strategy
Given the dependence of tumors on new blood vessel formation, scientists have developed anti-angiogenic therapies as a cancer treatment. These treatments aim to interfere with the process of angiogenesis, inhibiting the tumor’s ability to grow and spread by cutting off its blood supply. This strategy is often described as “starving” the tumor.
Anti-angiogenic drugs do not directly kill cancer cells; instead, they work by preventing or slowing the growth of the blood vessels that support the tumor. Many of these therapies specifically target the VEGF signaling pathway, as VEGF is a primary driver of tumor angiogenesis. Some anti-angiogenic drugs function as monoclonal antibodies that bind directly to VEGF, preventing it from activating its receptors on endothelial cells. This action stops the signals that promote blood vessel growth.
Other anti-angiogenic agents work by blocking the VEGF receptors, preventing them from receiving growth signals even if VEGF is present. These medications are often referred to as tyrosine kinase inhibitors (TKIs). The goal of these treatments is to slow or halt tumor progression, and they are frequently used in combination with other cancer therapies like chemotherapy or immunotherapy to enhance treatment effectiveness.