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Resistance to cetuximab in EGFR-overexpressing esophageal squamous cell carcinoma xenografts due to FGFR2 amplification and overexpression.
[esophageal carcinoma]
Esophageal
carcinoma
is
one
of
the
most
virulent
malignant
diseases
and
a
major
cause
of
cancer
-related
deaths
worldwide
.
Despite
improvements
in
surgical
techniques
and
perioperative
management
and
surgery
combined
with
chemotherapy
and
/
or
radiotherapy
,
the
prognosis
of
esophageal
squamous
cell
carcinoma
(
ESCC
)
at
an
advanced
stage
remains
poor
.
ESCC
shows
a
relatively
high
incidence
of
EGFR
(
50
%
-
70
%
)
,
and
the
humanized
monoclonal
antibody
(
mAb
)
cetuximab
against
EGFR
has
been
undergoing
clinical
development
.
However
,
all
responding
patients
eventually
developed
acquired
resistance
to
cetuximab
.
In
the
current
study
,
we
described
a
cetuximab-sensitive
ESCC
xeongraft
model
that
developed
resistance
to
cetuximab
as
a
result
of
FGFR
2
gene
amplification
and
overexpression
.
Inhibition
of
FGFR
2
signaling
in
this
xenograft
model
restored
its
sensitivity
to
cetuximab
.
The
antitumor
effect
may
be
induced
by
inhibition
of
AKT
phosphorylation
.
These
findings
suggest
that
combination
therapyincluding
cetuximab
and
FGFR
2
inhibition
may
be
a
promising
strategy
to
treat
ESCC
.
Diseases
Validation
Diseases presenting
"advanced stage"
symptom
carcinoma of the gallbladder
coats disease
dedifferentiated liposarcoma
erdheim-chester disease
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
inclusion body myositis
liposarcoma
oral submucous fibrosis
wiskott-aldrich syndrome
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