Colorectal adenocarcinoma-derived EGFR mutants are oncogenic and sensitive to EGFR-targeted monoclonal antibodies, cetuximab and panitumumab

Nayoung Kim, Daseul Cho, Hyunjin Kim, Sujin Kim, Young je Cha, Heidi Greulich, Adam Bass, Hyun Soo Cho, Jeonghee Cho

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Somatic mutations of epidermal growth factor receptor (EGFR) occur in ~3% of colorectal cancer (CRC) patients. Here, through systematic functional screening of 21 recurrent EGFR mutations selected from public data sets, we show that 11 colon cancer-derived EGFR mutants (G63R, E114K, R165Q, R222C, S492R, P596L, K708R, E709K, G719S, G724S and L858R) are oncogenic and able to transform cells in a ligand-independent manner. We demonstrate that cellular transformation by these mutants requires receptor dimerization. Importantly, the EGF-induced and constitutive oncogenic potential of these EGFR mutants are inhibited by cetuximab or panitumumab in vivo and in vitro. Taken together, we propose that a subset of EGFR mutations can serve as genomic predictors for response to anti-EGFR antibodies and that metastatic CRC patients with such mutations may benefit from these drugs as part of the first-line therapy.

Original languageEnglish
Pages (from-to)2194-2200
Number of pages7
JournalInternational Journal of Cancer
Volume146
Issue number8
DOIs
Publication statusPublished - 2020 Apr 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Colorectal adenocarcinoma-derived EGFR mutants are oncogenic and sensitive to EGFR-targeted monoclonal antibodies, cetuximab and panitumumab'. Together they form a unique fingerprint.

  • Cite this