endostatin

Endostatin monomer, basic amino acid residues shown in red 1KOE

Endostatin is a naturally-occurring 20-kDa C-terminal fragment derived from type XVIII collagen. It is reported to serve as an anti-angiogenic agent, similar to angiostatin and thrombospondin

Endostatin is a angiogenesis inhibitor. Endostatin is a broad spectrum angiogenesis inhibitor and may interfere with the pro-angiogenic action of growth factors such as basic fibroblast growth factor (bFGF/FGF-2) and vascular endothelial growth factor (VEGF).^[1]

Possible cancer treatment

Endostatin is currently being studied as part of cancer research.

Phase I

In a Phase I clinical trial of Endostatin of the 19 patients treated, 12 were switched out of the trial by their physicians due to continued progression of their disease.^[2] Two patients continued to be treated, and the remaining patients withdrew on their own. The trial, designed primarily to demonstrate safety, indeed showed that the drug was safe and well-tolerated (at the dosages used).

Phase II

In a Phase II clinical trial of Endostatin forty two patients with pancreatic endocrine tumors or carcinoid tumors were treated.^[3] Of the 40 patients which could be evaluated for a radiologic response, none experienced partial response to therapy, as defined by World Health Organization criteria.

The conclusion from the trial was that "Treatment with Endostatin did not result in significant tumor regression in patients with advanced neuroendocrine tumors."

Phase III

A phase III clinical trial was carried out on 493 histology or cytology confirmed stage IIIB and IV NSCLC patients with a life expectancy >3 months. Patients were treated with Endostar (rh-endostatin, YH-16) a recombinant endostatin product in combination with vinorelbine and cisplatin (a standard chemotherapeutic regimen). The addition of Endostar to the standard chemotherapeutic regimen in these advanced NSCLC patients resulted in significant and clinically meaningful improvement in response rate, median time to progression, and clinical benefit rate compared with the chemotherapeutic regimen alone ^[4]

Clinical significance

Down's syndrome patients seem to be protected from diabetic retinopathy due to their elevated levels of endostatin.^[5]

References

1. ^ Folkman, J. (2006). "Antiangiogenesis in cancer therapy--endostatin and its mechanisms of action". Exp. Cell. Res. 312: 594–607. doi:10.1016/j.yexcr.2005.11.015. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16376330&query_hl=23&itool=pubmed_docsum. 
2. ^ Dana-Farber Cancer Institute (November 2000). "Boston hospitals report early results of Endostatin clinical trial". Press release. http://www.dfci.harvard.edu/abo/news/pressarchive/110900.asp. Retrieved 2006-07-12.  BROKEN LINK
3. ^ Kulke M H et al. (2006). "Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors". J. Clin. Oncol. 24: 3555–3561. doi:10.1200/JCO.2006.05.6762. PMID 16877721. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16877721&query_hl=1&itool=pubmed_docsum. 
4. ^ Results of phase III trial of rh-endostatin (YH-16) in advanced non-small cell lung cancer (NSCLC) patients (Y. Sun, J. Wang, Y. Liu, X. Song, Y. Zhang, K. Li, Y. Zhu, Q. Zhou, L. You and C. Yao) [1]
5. ^ http://journals.lww.com/jcraniofacialsurgery/Abstract/2009/03001/Role_of_Endogenous_Angiogenesis_Inhibitors_in_Down.9.aspx

External links

• MeSH Endostatin
• http://video.google.ca/videoplay?docid=6419681728654132172&q=frontiers+of+medicine+duration%3Along
• PBS' Nova program explores Endostatin in 2001

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