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Current Oncology Reports

, 16:365 | Cite as

Endoglin for Targeted Cancer Treatment

  • Lee S. Rosen
  • Michael S. Gordon
  • Francisco Robert
  • Daniela E. Matei
Evolving Therapies (R Bukowski, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Evolving Therapies

Abstract

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.

Keywords

Endoglin 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 

Notes

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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Lee S. Rosen
    • 1
  • Michael S. Gordon
    • 2
  • Francisco Robert
    • 3
  • Daniela E. Matei
    • 4
  1. 1.Hematology-OncologyUCLA Medical Center Santa MonicaSanta MonicaUSA
  2. 2.Pinnacle Oncology HematologyScottsdaleUSA
  3. 3.Division of Hematology/OncologyUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Division of Hematology/OncologyIndiana University School of MedicineIndianapolisUSA

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