What is Endostatin?

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  • Written By: S. Gadd
  • Edited By: J.T. Gale
  • Last Modified Date: 17 October 2019
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Endostatin is the naturally generated C-terminal protein fragment that results from the proteolytic cleavage of the COL18A1 protein. Generally, it exhibits anti-angiogenic properties in the body. Also, it is being studied as an anti-cancer drug.

An adequate blood supply is a requirement of both normal tissues and tumors because it delivers nourishment and oxygen, and removes carbon dioxide (CO2) and cellular waste. Angiogenesis, or blood vessel formation, is triggered in tumors by the secretion of growth factors, such as fibroblast growth factors (FGFs), and angiogenic factors, such as vascular endothelial growth factor (VEGF). The release of these factors into the tumor environment leads to the growth of capillaries in tumors, providing nutrients that allow for tumor survival and growth. Therefore, compounds that act to inhibit angiogenesis have the potential to be potent inhibitors of tumor growth and metastasis.

The anti-angiogenic properties of endostatin were first reported in 1997 by the laboratory of Judah Folkman, MD, who found that this compound shrank tumors in mice by blocking the tumor’s blood supply. Clinical trials that began in the late 1990s reported that it arrested tumor growth in human subjects and greatly improved their quality of life. This was even true in patients where other treatments had failed.


Although endostatin arrested tumor growth, it failed to shrink the majority of tumors in patients, and therefore the results of these clinical trials were considered a disappointment. This news, coupled with the fact that endostatin was expensive to produce, led to a lack of interest in further production. It was not until a reformulation of the compound led to cheaper production – and this formulation of endostatin was approved in China in 2005 for the treatment of lung cancer – that interest once again began to surge. It is being studied as a cancer treatment in combination with other cancer drugs.

Endostatin has several advantages over conventional cancer treatments. Since it is produced naturally by the body and functions to modify only those cells that line blood vessels, reports of toxicity are low. In addition, because reports indicate that it resulted in tumor dormancy even after multiple cycles of treatment, it is thought that it does not induce drug resistance, a common problem with other cancer treatments.

Angiostatin and the thrombospondins are other naturally occurring compounds that also show promise as anti-angiogenic drugs. Angiostatin is a proteolytic cleavage product of the blood clotting factor plasminogen. The thrombospondins are a family of secreted proteins that inhibit angiogenesis via several mechanisms, the most widely studied of which is the ability of thrombospondins to decrease the cellular response to VEGF. Both angiostatin and thrombospondin show the ability to inhibit angiogenesis in tumor development, and may be promising drugs for cancer treatment.

Endostatin is also being studied as a treatment for two serious disorders of the eye: diabetic retinopathy and the wet form of macular degeneration. Both of these conditions arise from the formation of new blood vessels in areas where they do not usually grow. These blood vessels are often weak and leaky, resulting in fluid accumulation and deteriorating vision. Similar to tumor angiogenesis, these changes are often associated with cellular release of VEGF, and endostatin is therefore being considered as a possible treatment for these conditions.


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