Endoglin for targeted cancer treatment topical collection on evolving therapies

Lee S. Rosen, Michael S. Gordon, Francisco Robert, Daniela E. Matei

Research output: Contribution to journalArticle

48 Scopus citations

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.

Original languageEnglish (US)
Article number365
JournalCurrent oncology reports
Volume16
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Angiogenesis
  • Antibody
  • Antibody-drug conjugate
  • Bone morphogenic protein
  • CD105
  • Endoglin
  • Glioblastoma
  • Hepatocellular cancer
  • Hypoxia
  • Prostate cancer
  • Radioimmunoconjugate
  • Renal cell cancer
  • Sarcoma
  • Transforming growth factor β
  • TRC105
  • Vascular endothelial growth factor resistance

ASJC Scopus subject areas

  • Oncology

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