Endoglin for Targeted Cancer Treatment
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Endoglin is a homodimeric cell membrane glycoprotein receptor for transforming growth factor β and bone morphogenetic proteins. Endoglin is essential for angiogenesis, being densely expressed on proliferating endothelial cells and upregulated during hypoxia. Its expression is implicated in development of resistance to vascular endothelial growth factor (VEGF) inhibition. TRC105 is an antibody that binds endoglin and prevents endothelial cell activation. Targeting endoglin and the VEGF pathway concurrently improves treatment in vitro and appears to reverse resistance to bevacizumab in some refractory cancer patients. Randomized trials are under way to assess the clinical benefit of adding TRC105 therapy to bevacizumab therapy. Further trials are under way to assess the activity of TRC105 with small-molecule inhibitors of the VEGF pathway in renal cell carcinoma, hepatocellular carcinoma, and soft tissue sarcoma. Stratification of soft tissue sarcomas based on endoglin expression levels is proposed to identify patients most likely to benefit from TRC105 treatment. The development of a TRC105 antibody–drug conjugate is also described.
KeywordsEndoglin CD105 TRC105 Angiogenesis Vascular endothelial growth factor resistance Antibody–drug conjugate Hypoxia Bone morphogenic protein Transforming growth factor β Antibody Radioimmunoconjugate Renal cell cancer Sarcoma Glioblastoma Prostate cancer Hepatocellular cancer
Compliance with Ethics Guidelines
Conflict of Interest
Lee S. Rosen received funding from Tracon Pharma for a clinical trial.
Michael S. Gordon, Francisco Robert, and Daniela E. Matei declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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