TBK1 Activation by VHL Loss in Renal Cell Carcinoma: A Novel HIF-Independent Vulnerability

Cancer Discov. 2020 Mar;10(3):348-350. doi: 10.1158/2159-8290.CD-19-1525.


The Von Hippel-Lindau gene product is a tumor suppressor whose ubiquitin ligase function is key to oxygen-sensing in cells, whereas Tank-binding kinase (TBK1) is a kinase mostly implicated in innate immune response. The study by Hu and colleagues in this issue reveals that VHL suppresses TBK1 activity under normoxic conditions, and that loss of VHL in kidney cancer cells renders them sensitive to TBK1 inhibition, providing a new potential target for the treatment of clear cell renal cell carcinoma.See related article by Hu et al., p. 460.

Publication types

  • Comment

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Genes, Tumor Suppressor
  • Humans
  • Kidney Neoplasms* / genetics
  • Ligases
  • Protein Serine-Threonine Kinases
  • Ubiquitin-Protein Ligases / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein


  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Protein Serine-Threonine Kinases
  • TBK1 protein, human
  • Ligases
  • VHL protein, human