Angiogenesis is the process where new blood vessels sprout from existing ones. While essential for normal bodily functions like growth and repair, it also contributes to the progression of diseases, especially cancer development and its spread.
Angiogenesis in a Healthy Body
In a healthy individual, angiogenesis is a tightly controlled process that occurs in specific situations to support physiological needs. During embryonic and fetal development, it forms and grows organs and tissues. It also aids wound healing by supplying oxygen and nutrients to damaged tissues, facilitating their repair.
The female reproductive cycle also demonstrates controlled angiogenesis, such as in the regeneration of the uterine lining after menstruation. This process is precisely regulated by a balance of stimulating and inhibiting factors, ensuring vessel growth occurs only when and where needed.
How Cancer Exploits Angiogenesis
Small tumors, less than 1-2 millimeters in diameter, can initially survive by obtaining nutrients and oxygen from nearby existing blood vessels through diffusion. As a tumor grows beyond this size, the inner cells become deprived of oxygen and nutrients, leading to a state of hypoxia. This oxygen deprivation triggers a shift known as the “angiogenic switch,” where the tumor begins to promote its own blood supply.
Cancer cells, in response to the hypoxic environment, release specific molecular signals that stimulate angiogenesis. One of the most prominent of these signals is Vascular Endothelial Growth Factor (VEGF), a protein that binds to receptors on endothelial cells, the cells lining blood vessels. This binding stimulates these endothelial cells to proliferate and migrate, initiating the sprouting of new capillaries from existing blood vessels towards the tumor.
The newly formed blood vessels are structurally and functionally abnormal compared to healthy vessels; they are leaky, tortuous, and have irregular diameters. This chaotic network forms a lifeline for the tumor, providing it with a continuous supply of oxygen and nutrients for rapid growth and proliferation. Furthermore, these abnormal vessels offer a direct pathway for cancer cells to escape the primary tumor, enter the bloodstream, and travel to distant organs, a process known as metastasis.
Targeting Angiogenesis in Cancer Treatment
Targeting angiogenesis in cancer treatment, known as anti-angiogenic therapy, aims to inhibit or block the formation of new blood vessels that feed tumors. The primary goal of these therapies is to “starve” the tumor by cutting off its blood supply, thereby limiting its growth and preventing its spread. This approach is a strategy in cancer management.
One common approach involves blocking the activity of specific growth factors, such as VEGF, which stimulate vessel growth. Drugs designed for this purpose, often monoclonal antibodies or small molecule inhibitors, either bind directly to VEGF, preventing it from interacting with its receptors, or block the receptors on endothelial cells themselves. This disruption prevents the signaling cascade that would otherwise lead to new vessel formation.
The intended outcomes of anti-angiogenic treatments are multifaceted. By normalizing or pruning the tumor’s existing blood vessels, these therapies can inhibit tumor growth and reduce the likelihood of metastasis. They can also make the tumor environment more amenable to other treatments like chemotherapy or radiation therapy, by improving the delivery of drugs and oxygen to the tumor cells. Anti-angiogenic therapies are frequently used in combination with standard cancer treatments, and ongoing research continues to explore new targets and refine their application to improve patient outcomes.