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Colorectal adenocarcinoma‐derived EGFR mutants are oncogenic and sensitive to EGFR‐targeted monoclonal antibodies, cetuximab and panitumumab
Author(s) -
Kim Nayoung,
Cho Daseul,
Kim Hyunjin,
Kim Sujin,
Cha Youngje,
Greulich Heidi,
Bass Adam,
Cho HyunSoo,
Cho Jeonghee
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32499
Subject(s) - panitumumab , cetuximab , monoclonal antibody , colorectal adenocarcinoma , adenocarcinoma , epidermal growth factor receptor , medicine , cancer research , mutant , monoclonal , colorectal cancer , kras , antibody , oncology , biology , immunology , cancer , gene , genetics
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.