VEGF Biomarker

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What is the VEGF pathway?

Inside your body, your cells communicate with each other in a way that’s a bit like a game of telephone. One important message they can share is about building new blood vessels, which are tiny tubes that carry blood to different parts of your body. This process is called angiogenesis, and it’s usually well-controlled, happening only when your body really needs new blood vessels, like for healing a cut. 

In healthy individuals, angiogenesis is a regulated process, occurring only when necessary. 

In colorectal cancer, something goes off track. A protein called vascular endothelial growth factor (VEGF), which is like a special code for starting the ‘build new blood vessels’ message, gets overly active. It’s like someone in the telephone game keeps repeating the message too loudly or too often. This causes too many new blood vessels to form. 

VEGF is a signaling protein that sticks to its receptor, VEGFR, on the surface of cells. It may be helpful to think of this binding reaction like a lock and key. In this scenario, VEGF is the key and VEGFR is the lock. VEGF is the key that can “unlock” the VEGF receptor (VEGFR). When VEGF binds to its receptor (VEGFR), or “unlocks” it, the receptor is turned “on.”  

Why is this a problem?

Cancer cells are greedy; they want more food and oxygen to grow, and they get these from blood. By triggering the growth of new blood vessels, cancer is essentially building its own supply lines, getting the nourishment it needs to grow and potentially spread. 

In colorectal cancer, the overexpression of VEGF or its receptor (VEGFR) disrupts this balance. The tumor exploits the VEGF signaling pathway to promote the formation of new blood vessels, creating a supply network for itself. These blood vessels provide the tumor with essential nutrients and oxygen, which are necessary for its growth and survival. 

Understanding this process helps doctors figure out how to treat cancer. They can work on ways to interrupt this message, sort of like putting a stop to the game of telephone, which can slow down the cancer’s growth and limit its ability to spread. 

What are angiogenesis inhibitors?

Angiogenesis inhibitors are a class of targeted therapies that work by decreasing VEGF expression or blocking the VEGF receptor (VEGFR) to prevent the formation of new blood vessels and limit tumor growth.  

Remember the ‘game of telephone’ your cells play to create new blood vessels? In colorectal cancer, this game can get out of hand, leading to more blood vessels feeding the tumor. Angiogenesis inhibitors aim to interrupt this process. 

Without a blood supply, the tumor is “starved” of oxygen and nutrients, resulting in slow tumor growth. Bevacizumab and fruquintinib are FDA-approved angiogenesis inhibitors for the treatment of metastatic colorectal cancer.  

Fruquintinib is a tyrosine kinase inhibitor (TKI) that works by blocking the VEGF receptor (VEGFR). VEGFR is an example of a TKI and fruquintinib inhibits or disrupts its signaling activity. The cells won’t even get the instruction to build these cancer-feeding blood vessels. 

Both therapies inhibit angiogenesis, or the formation of new blood vessels, to “starve” and slow the growth of the tumor. Without new blood vessels, the tumor can’t get the oxygen and nutrients it needs to grow quickly. This means the tumor’s growth can be slowed down significantly. 

Who are angiogenesis inhibitors for?

Currently, all FDA-approved angiogenesis inhibitors for the treatment of colorectal cancer are for patients with stage IV—metastatic disease. This means the cancer has spread beyond the original site in the colon or rectum to other parts of the body. 

It’s important to remember that the most effective treatment can differ from person to person. What works best for you might be different from what works for someone else. That’s why it’s really important to talk with your medical team. They understand your unique situation and can guide you through the options to find the best treatment plan for you. 

How to find Clinical Trials evaluating VEGF and VEGFR

Check out Fight CRC’s Clinical Trial Finder and our blog series, Clinical Trial Conversations, to research and discover more. 

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