Colorectal adenocarcinoma-derived EGFR mutants are oncogenic and sensitive to EGFR-targeted monoclonal antibodies, cetuximab and panitumumab.
Nayoung KimDaseul ChoHyunjin KimSujin KimYoung-Je ChaHeidi GreulichAdam BassHyun-Soo ChoJeonghee ChoPublished in: International journal of cancer (2019)
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.
Keyphrases
- epidermal growth factor receptor
- small cell lung cancer
- tyrosine kinase
- advanced non small cell lung cancer
- wild type
- squamous cell carcinoma
- healthcare
- end stage renal disease
- transcription factor
- mental health
- emergency department
- machine learning
- metastatic colorectal cancer
- radiation therapy
- gene expression
- electronic health record
- prognostic factors
- peritoneal dialysis
- oxidative stress
- rectal cancer
- risk assessment
- cell proliferation
- cell cycle arrest
- patient reported outcomes
- smoking cessation
- cancer therapy
- adverse drug