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What is VEGF?

Vascular endothelial growth factor (VEGF) is a signalling protein that promotes the growth of new blood vessels.

VEGF forms part of the mechanism that restores the blood supply to cells and tissues when they are deprived of oxygenated blood due to compromised blood circulation. Functions One of the main functions of VEGF is to form new blood vessels as a baby grows and develops in the womb.

This protein also stimulates the growth of new blood vessels after injury and the growth of muscle after exercise has been performed. In cases where blood vessels are obstructed, VEGF also promotes the creation of new blood vessels to bypass the blocked vessels.

Problems with VEGF The overexpression of VEGF is a contributing factor to the development of disease.

For example, solid tumors require an increased blood supply if they are to continue growing beyond a certain size and tumors that express VEGF are able to continue growing because they can develop this enhanced blood supply, a process referred to as angiogenesis. Cancers that express VEGF are therefore able to grow and spread (metastasize) to other organs and regions of the body.

The overexpression of VEGF can also lead to vascular disease in the retina and other body parts. Expression of this protein has also been associated with a poor outcome in and pulmonary emphysema. A decreased level of VEGF in the pulmonary arteries has been associated with the condition pulmonary emphysema. Since cancer growth is stimulated by VEGF, researchers have made numerous attempts to decrease its expression to prevent angiogenesis and tumor growth. If the blood supply is reduced, the tumor is literally “starved” to death.

Two drugs that have been successful at slowing the progression of diseases that rely on VEGF are bevacizumab and ranibizumab. 

 

Diseases related to VEGF

There are a number of diseases and conditions that are associated with or related to VEGF.

These are all diseases that involve an overgrowth of blood vessels. Below is a list of these diseases and conditions, followed by a short explanation of each one. Cancer Cancers that express VEGF are therefore able to grow and spread (metastasize) to other organs and regions of the body. While it is normal for the blood vessels to form around a tumor to nourish it, in some cases the blood vessels continue to grow in an uncontrolled manner. This is known as angiogenesis. When this occurs, the cancer is able to grow beyond its original size and invade surrounding tissue or other organs. If the new blood vessels are able to form sufficient connections with pre-existing blood vessels, the cancer is then able to continue to receive the nutrients and growth factors it requires to thrive. This process allows solid tumors to increase in size, invade surrounding tissue and metastasize (spread) to other parts of the body.

Tumors that have the ability to spread are often described as malignant. In cases where angiogenesis does not occur or is limited, the tumor is able to grow beyond a certain size and will eventually stop growing, but it is not able to spread. These tumors are referred to as benign. This means that it is possible for tumors to be malignant (cancerous) without being invasive. One of the key goals of oncology (cancer treatment) is to stop angiogenesis or at least limit it so that the tumor remains benign. The table below provides a brief overview of some cancers that have been shown to be influenced by VEGF.

Cancer type Description Small Cell Lung Carcinoma (SCLC) SCLC is a cancer that originates in the lungs and accounts for 15% of all lung cancer cases.

These tumors usually appear in the central part of the lungs. They have a tendency to spread very quickly and do not respond well to chemotherapy or other medical therapies. Despite recent advances in targeted therapy, the prognosis for SCLC remains poor. The exact cause for SCLC is unknown, but some evidence suggests that this cancer type may be related to smoking or other forms of air pollution. Large Cell Lung Carcinoma (Pancreatic) Similar to SCLC, the cause of this cancer type is unknown. It is possible that this cancer is also related to smoking or other forms of air pollution. Large cell lung carcinomas typically appear in the central part of the lungs, but may appear in the peripheral regions as well. As with SCLC, the prognosis for patients is very poor and most die within a year after being diagnosed. This cancer is also known to spread quickly and invade surrounding tissue and organs.

While some large cell lung carcinomas are susceptible to chemotherapy, most are not. Merkel Cell Carcinoma (Melanoma) Merkel cell carcinomas are a type of skin cancer that most often affect older adults (ages 50-70). These tumors can appear anywhere on the body, but they have a tendency to develop on the limbs and trunk. Merkel cell carcinomas rarely spread to other parts of the body. They are also slow growing and can remain in an early stage for years without ever spreading. Even when they do spread, they are still limited to the local region where they originated. As with most skin cancers, early detection is key and treatment is often easier when it’s caught in the earlier stages. Despite this, many people do not seek medical attention until the cancer is already in an advanced stage. The prognosis for patients with this type of skin cancer depends on a variety of factors including how far the cancer has spread and whether it has metastasized to other organs. Some forms of treatment include chemotherapy and immunotherapy, but some may also require surgery. As with most skin cancers, prevention is key and it’s always better to catch it early. Colon and Rectal Cancers (Colorectal) These types of cancer can develop in either the colon or the rectum, but both are often treated similarly. The most common risk factor for developing colorectal cancer is age.

As people get older, they are at higher risk of developing these types of cancer. It is also more common in men than women and those who have a family history of colorectal cancer are also at a higher risk of developing it.

Colorectal cancer is a slow growing cancer and does not always cause noticeable symptoms in its early stages. However, as the disease progresses, patients may experience symptoms such as abdominal pain, fatigue, change in bowel habits, or blood in the stool. Despite being a common type of cancer and having no known cause, the survival rate for this type of cancer is quite high. The five-year survival rate for people with localized cancer that has not spread to other parts of the body is 90%. The five-year survival rate for people with regional spread of the cancer is about 70% and the five-year survival rate for people with distant spread of the cancer is about 16%. Pancreatic Cancers (Pancreatic) There are several types of pancreatic cancer, but most are rare. The most common type is pancreatic adenocarcinoma and it usually affects patients in their 50s or 60s.

The pancreas is a glandular organ that lies near the stomach and helps with digestion. A majority of the time, pancreatic cancer starts in the cells that produce enzymes for digestion. The pancreas is located deep within the abdomen, which makes it difficult for physicians to detect pancreatic tumors early on. There are no reliable screening tests for pancreatic cancer and most patients are diagnosed in an advanced stage. Treatment options are often limited and surgery is rarely an option due to the inaccessibility of the pancreas. There are different types of treatment available and most are aimed at relieving pain and extending life. The five-year survival rate for people with pancreatic adenocarcinoma that has spread to other parts of the body is 4%.

Pancreatic cancer is usually diagnosed in an advanced stage and has a very poor prognosis. Even when detected early, the five-year survival rate is still only about 20%. There are no reliable screening tests for pancreatic cancer and most patients are diagnosed in an advanced stage.

Treatment options are often limited and surgery is rarely an option due to the inaccessibility of the pancreas. There are different types of treatment available and most are aimed at relieving pain and extending life.

 

Source:

Vascular endothelial growth factor (VEGF) and its receptors (G Neufeld, T Cohen, S Gengrinovitch… – The FASEB …, 1999 – Wiley Online Library)
https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fasebj.13.1.9

The biology of VEGF and its receptors (N Ferrara, HP Gerber, J LeCouter – Nature medicine, 2003 – nature.com)
https://www.nature.com/articles/nm0603-669

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