endostatin

Endostatin is a potent endogenous inhibitor of angiogenesis, a 20-kilodalton C-terminal fragment of collagen XVIII. It was identified in 1997 by O’Reilly and colleagues as an inhibitor of endothelial cell proliferation and tumor growth, highlighting its potential to slow or halt tumor vascularization.

Endostatin acts through multiple mechanisms. It inhibits endothelial cell proliferation and migration, can induce apoptosis of endothelial cells, and interferes with several pro-angiogenic signaling pathways, including VEGF and fibroblast growth factor signaling. It also interacts with endothelial integrins such as α5β1 and αvβ3, and with heparan sulfate proteoglycans, contributing to its anti-angiogenic activity.

Biochemically, endostatin corresponds to a fragment derived from the NC1 domain at the C-terminus of type XVIII collagen. It is generated by proteolytic processing of collagen XVIII by proteases such as matrix metalloproteinases, and several recombinant or synthetic forms have been studied for therapeutic use.

Clinical development has explored endostatin as an anti-angiogenic cancer therapy. Recombinant human endostatin has undergone various clinical trials, and in China a form marketed as Endostar has been used for non-small cell lung cancer. Trials have reported mixed results, with some indications of improved progression-free survival when combined with chemotherapy, while overall survival benefits remain uncertain. Adverse effects are generally mild but can include fatigue and infusion-related reactions.

Research continues to improve pharmacokinetics and delivery, including strategies such as fusion proteins and other modifications to extend half-life and bioavailability, with ongoing evaluation in oncology and related fields.