Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L

Nat Commun. 2023 Apr 26;14(1):2407. doi: 10.1038/s41467-023-36910-5.

Abstract

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. These findings implicate CD5L as an important factor in adaptive resistance to antiangiogenic therapy and suggest that modalities to target CD5L have potentially important clinical utility.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis Regulatory Proteins
  • Bevacizumab / pharmacology
  • Bevacizumab / therapeutic use
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Receptors, Scavenger
  • Vascular Endothelial Growth Factor A* / genetics
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Antibodies, Monoclonal
  • Angiogenesis Inhibitors
  • CD5L protein, human
  • Apoptosis Regulatory Proteins
  • Receptors, Scavenger