Reactions 1680, p151 - 2 Dec 2017
Development of acquired resistance: case report
A patient [age and sex not stated] received gefitinib for lung
adenocarcinoma and developed acquired resistance to
The patient, who had a history of lung adenocarcinoma, was
started on gefitinib [route and dosage not stated]. A cell growth
inhibition test was performed with gefitinib and afatinib. The
lung adenocarcinoma cell line (G719S-GR) was established
from the malignant pleural effusion. The test showed human
epidermal growth factor receptor-tyrosine kinase inhibitors
(EGFR-TKI) resistance in G719S-GR cells with an LC50 of
greater than 100µM for either afatinib or gefitinib [time to
reaction onset not stated], and indicated that the tumour
developed an acquired resistance from the initial treatment
with gefitinib. The test result also showed the G719S-GR cells
resistant to EGFR-TKI in vitro. The next generation sequencing
(NGS) revealed G719S-GR cells harbor EGFR mutations of
E709A and G719S along with the amplification of EGFR, MYC,
interleukin 7 receptor (IL7R) and fibroblast growth factor
receptor 1 (FGFR1) locus. Additionally, the loss of tuberous
sclerosis 1 (TSC1), phosphatase and tensin homolog (PTEN)
and cyclin-dependent kinase inhibitor 2A (CDKN2A) were
observed in G719S-GR cells.
The loss PTEN was considered to be the mechanism for the
development of acquired resistance to gefitinib.
Author comment: "We established a lung adenocarcinoma
cell line (G719S-GR) from the malignant pleural effusion of a
patient whose tumor developed acquired resistance from
initial treatment with gefitinib."
Osoegawa A, et al. Acquired resistance to EGFR-TKI in an uncommon G719S
EGFR mutation. Cancer Research 77 (Suppl. 13): abstr. 4107, No. 13, Jul 2017.
Available from: URL: http://doi.org/10.1158/1538-7445.AM2017-4107 [abstract] -
Reactions 2 Dec 2017 No. 16800114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved