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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
"squamous cell carcinoma"
symptom
carcinoma of the gallbladder
child syndrome
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
junctional epidermolysis bullosa
kallmann syndrome
kindler syndrome
liposarcoma
monosomy 21
oculocutaneous albinism
oral submucous fibrosis
papillon-lefèvre syndrome
This symptom has already been validated