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Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L.

Christopher J LaFarguePaola AmeroKyunghee NohLingegowda S MangalaYunfei WenEmine BayraktarSujanitha UmamaheswaranElaine SturSantosh K DasariCristina IvanSunila PradeepWonbeak YooChunhua LuNicholas B JenningsVinod VathipadiekalWei HuAnca Chelariu-RaicuZhiqiang KuHui DengWei XiongHyun-Jin ChoiMin HuTakae KiyamaChai-An MaoRouba Ali-FehmiMichael J BirrerJinsong LiuNingyan ZhangGabriel Lopez-BeresteinVittorio de FranciscisZhiqiang AnAnil K Sood
Published in: Nature communications (2023)
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.
Keyphrases
  • vascular endothelial growth factor
  • nk cells
  • endothelial cells
  • poor prognosis
  • cell proliferation
  • cancer therapy
  • drug delivery
  • binding protein
  • free survival
  • magnetic nanoparticles