Colorectal adenocarcinoma-derived EGFR mutants are oncogenic and sensitive to EGFR-targeted monoclonal antibodies, cetuximab and panitumumab
- Authors
- Kim, N[Kim, Nayoung]; Cho, D[Cho, Daseul]; Kim, H[Kim, Hyunjin]; Kim, S[Kim, Sujin]; Cha, YJ[Cha, Young-je]; Greulich, H[Greulich, Heidi]; Bass, A[Bass, Adam]; Cho, HS[Cho, Hyun-Soo]; Cho, J[Cho, Jeonghee]
- Issue Date
- Apr-2020
- Publisher
- WILEY
- Keywords
- epidermal growth factor receptor (EGFR); cetuximab (Erbitux); panitumumab; colon cancer; EGFR mutation; receptor dimerization; targeted therapy
- Citation
- INTERNATIONAL JOURNAL OF CANCER, v.146, no.8, pp.2194 - 2200
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF CANCER
- Volume
- 146
- Number
- 8
- Start Page
- 2194
- End Page
- 2200
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/16098
- DOI
- 10.1002/ijc.32499
- ISSN
- 0020-7136
- Abstract
- Somatic mutations of epidermal growth factor receptor (EGFR) occur in similar to 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.
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