The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

Cancer Cell. 2019 Jan 14;35(1):125-139.e9. doi: 10.1016/j.ccell.2018.11.018.


The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the molecular underpinnings of this transmissible cancer, we combined pharmacological screens with an integrated systems-biology characterization. Sensitivity to inhibitors of ERBB tyrosine kinases correlated with their overexpression. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to the evolutionary conserved oncogenic STAT3. ERBB inhibition blocked phosphorylation of STAT3 and arrested cancer cells. Pharmacological blockade of ERBB or STAT3 prevented tumor growth in xenograft models and restored MHC class I expression. This link between the hyperactive ERBB-STAT3 axis and major histocompatibility complex class I-mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and puts forward a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD. VIDEO ABSTRACT.

Keywords: ERBB; MHC class I; STAT3; Tasmanian devil; horizontal transmission; receptor tyrosine kinases; systems biology; transmissible cancer; tumor vulnerability; xenograft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Methylation
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / metabolism*
  • Facial Neoplasms / drug therapy*
  • Facial Neoplasms / metabolism
  • Facial Neoplasms / veterinary*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histocompatibility Antigens Class I / metabolism
  • Marsupialia
  • Mice
  • Phosphorylation
  • Proteomics / methods*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Small Molecule Libraries / administration & dosage*
  • Small Molecule Libraries / pharmacology
  • Xenograft Model Antitumor Assays


  • Histocompatibility Antigens Class I
  • STAT3 Transcription Factor
  • Small Molecule Libraries
  • ErbB Receptors