Endostatin

Summary

Endostatin is an endogenous anti-angiogenic peptide derived from collagen XVIII, originally identified by Judah Folkman's group. It inhibits tumor growth by starving tumors of their blood supply. Recombinant forms have been investigated in clinical trials for various cancers. A recombinant human endostatin (Endostar/YH-16) was approved in China for non-small cell lung cancer.

Mechanism of Action

Endostatin is a 20 kDa C-terminal fragment of collagen XVIII that inhibits angiogenesis by binding to heparan sulfate proteoglycans and integrins (αvβ3, αvβ5, α5β1), blocking endothelial cell migration, proliferation, and tube formation; it also downregulates VEGF signaling and promotes apoptosis of endothelial cells.

Routes of Administration

Goals & Uses

• Ocular neovascularization (wet AMD)OphthalmologyLow
• Colorectal cancer treatmentOncologyLow
• Non-small cell lung cancer treatmentOncologyModerate
• Breast cancer treatmentOncologyLow
• Anti-tumor angiogenesis inhibitionOncologyModerate

Contraindications

• Active hemorrhage or coagulopathyHematologicModerate
• Severe hepatic impairmentOrganModerateLiver function concerns
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Hypersensitivity to endostatin or excipientsAllergy / ImmunologyHigh

Adverse Effects

• Nausea / VomitingGastrointestinalUncommon
• HypertensionCardiovascularUncommonHigh blood pressure
• Injection site reactionsLocalCommon
• FatigueGeneralCommonLow energy or tiredness
• Elevated liver enzymes (transaminases)HepaticUncommon
• ThromboembolismCardiovascularRare

Drug Interactions

• Other anti-angiogenic agents (bevacizumab, sunitinib)Moderate
• Anticoagulants (warfarin, heparin)Moderate
• Vinorelbine / Cisplatin (NP regimen)Moderate

Population Constraints

• Pediatric patientsAgeRelative
• Breastfeeding womenReproductiveRelative
• Patients with active bleeding disordersHematologicRelative
• Pregnant womenReproductiveAbsolute

Regulatory Status

• European UnionInvestigationalNo EMA approval; remains in early-phase research settings.
• United StatesInvestigationalNot FDA approved; studied in Phase I/II oncology trials. No active NDA/BLA on record.
• United KingdomInvestigationalNo MHRA approval; investigational status consistent with EU.

Recombinant human endostatin (Endostar, rh-endostatin) received approval from the Chinese State Food and Drug Administration (SFDA, now NMPA) in 2005 for non-small cell lung cancer in combination with chemotherapy. It has not received FDA or EMA approval. Trials in the US and Europe remain at investigational status.

Evidence & Sources

No sources recorded yet.