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Endoglin for Targeted Cancer Treatment

  • Evolving Therapies (R Bukowski, Section Editor)
  • Published:
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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.

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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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Authors and Affiliations

  1. Hematology-Oncology, UCLA Medical Center Santa Monica, 2020 Santa Monica Blvd, Ste 600, Santa Monica, CA, 90404, USA

    Lee S. Rosen

  2. Pinnacle Oncology Hematology, 9055 E. Del Camino, Ste 100, Scottsdale, AZ, 85258, USA

    Michael S. Gordon

  3. Division of Hematology/Oncology, University of Alabama at Birmingham, 1824 6th Ave South, WTI-210, Birmingham, AL, 35294, USA

    Francisco Robert

  4. Division of Hematology/Oncology, Indiana University School of Medicine, 980 W. Walnut St, R3 C218D, Indianapolis, IN, 46202, USA

    Daniela E. Matei

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  1. Lee S. Rosen
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Correspondence to Lee S. Rosen.

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Rosen, L.S., Gordon, M.S., Robert, F. et al. Endoglin for Targeted Cancer Treatment. Curr Oncol Rep 16, 365 (2014). https://doi.org/10.1007/s11912-013-0365-x

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