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Amphiregulin can predict treatment resistance to palliative first-line cetuximab plus FOLFIRI chemotherapy in patients with RAS wild-type metastatic colorectal cancer
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Amphiregulin can predict treatment resistance to palliative first-line cetuximab plus FOLFIRI chemotherapy in patients with RAS wild-type metastatic colorectal cancer
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Amphiregulin can predict treatment resistance to palliative first-line cetuximab plus FOLFIRI chemotherapy in patients with RAS wild-type metastatic colorectal cancer
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Journal Article
Amphiregulin can predict treatment resistance to palliative first-line cetuximab plus FOLFIRI chemotherapy in patients with RAS wild-type metastatic colorectal cancer
2021
Overview
Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand. The aim of this study was to investigate the effects of baseline plasma AREG levels in
KRAS
,
NRAS
, and
BRAF
wild-type metastatic colorectal cancer (CRC) on treatment outcome with palliative first-line cetuximab + FOLFIRI chemotherapy. Chemotherapy outcomes were analyzed based on baseline plasma AREG levels. The clinical findings were further validated using an in vitro model of CRC. Among 35 patients, the progression-free survival (PFS) was significantly inferior in patients with high AREG than in those with low AREG levels: 10.9
vs
. 24.2 months, respectively (
p
= 0.008). However, after failure of first-line chemotherapy, AREG levels were associated with neither PFS (4.8
vs.
11.6 months;
p
= 0.215) nor overall survival (8.4
vs.
13.3 months;
p
= 0.975). In SNU-C4 and Caco-2 cells which were relatively sensitive to cetuximab among the seven CRC cell lines tested, AREG significantly decreased the anti-proliferative effect of cetuximab (
p
< 0.05) via AKT and ERK activation. However, after acquiring cetuximab resistance with gradual exposure for more than 6 months, AREG neither increased colony formation nor activated AKT and ERK after cetuximab treatment. Our results suggest that plasma AREG is a potential biomarker to predict clinical outcomes after cetuximab-based chemotherapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Adult
/ Aged
/ Antineoplastic Combined Chemotherapy Protocols - adverse effects
/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use
/ Camptothecin - adverse effects
/ Camptothecin - analogs & derivatives
/ Camptothecin - therapeutic use
/ Cetuximab - administration & dosage
/ Colorectal Neoplasms - blood
/ Colorectal Neoplasms - diagnosis
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - etiology
/ Fluorouracil - adverse effects
/ Fluorouracil - therapeutic use
/ Humanities and Social Sciences
/ Humans
/ Leucovorin - adverse effects
/ Leucovorin - therapeutic use
/ Male
/ Patients
/ Science
