Differential escape mechanisms in cetuximab-resistant head and neck cancer cells

Christopher D. Willey, Joshua C. Anderson, Hoa Q. Trummell, Faris Naji, Rik de Wijn, Eddy S. Yang, Markus Bredel, Nanda K. Thudi, James A. Bonner

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Acquired cetuximab resistance is a challenge for oncologists treating advanced head and neck carcinoma (HNC). While intrinsic cetuximab resistance mechanism in colorectal cancer is known, resistance in HNC is unclear. We established two different cetuximab resistant HNC cell lines by culturing epidermal growth factor (EGFR) expressing UM–SCC–1 and UM–SCC–6 cell lines in the presence of 5 μg/ml cetuximab. We then explored potential mechanisms of resistance. We found that the 2 cell lines developed resistance by different mechanisms. Specifically, we found that UM–SCC–1 resistant cells (UM–SCC–1R) showed enhanced EGF-induced downstream signals while UM–SCC–6 resistant cells (UM–SCC–6R) demonstrated EGF-independent signaling. Global kinase activity (kinomic) profiling revealed unique signaling differences in the two resistant cell lines. However, both of the resistant lines demonstrated increased phospho-serine 727 and total STAT3 expression compared to the parental lines. STAT3 knockdown promoted increased cytotoxicity both in the presence and absence of cetuximab in the resistant lines suggesting that STAT3 may be a common target in cetuximab resistance.

Original languageEnglish
Pages (from-to)36-42
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Sep 10 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.


  • Cetuximab
  • Epidermal growth factor receptor
  • Head and neck cancer
  • Kinomic profiling
  • STAT3

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Differential escape mechanisms in cetuximab-resistant head and neck cancer cells'. Together they form a unique fingerprint.

Cite this