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Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma.
[esophageal adenocarcinoma]
Esophageal
adenocarcinoma
ranks
sixth
in
cancer
mortality
in
the
world
and
its
incidence
has
risen
dramatically
in
the
Western
population
over
the
last
decades
.
Data
presented
herein
strongly
suggest
that
Notch
signaling
is
critical
for
esophageal
adenocarcinoma
and
underlies
resistance
to
chemotherapy
.
We
present
evidence
that
Notch
signaling
drives
a
cancer
stem
cell
phenotype
by
regulating
genes
that
establish
stemness
.
Using
patient-derived
xenograft
models
,
we
demonstrate
that
inhibition
of
Notch
by
gamma-secretase
inhibitors
(
GSI
)
is
efficacious
in
downsizing
tumor
growth
.
Moreover
,
we
demonstrate
that
Notch
activity
in
a
patient
's
ultrasound-assisted
endoscopic-derived
biopsy
might
predict
outcome
to
chemotherapy
.
Therefore
,
this
study
provides
a
proof
of
concept
that
inhibition
of
Notch
activity
will
have
efficacy
in
treating
esophageal
adenocarcinoma
,
offering
a
rationale
to
lay
the
foundation
for
a
clinical
trial
to
evaluate
the
efficacy
of
GSI
in
esophageal
adenocarcinoma
treatment
.
Cancer
Res
;
74
(
21
)
;
6364
-
74
.
©
2014
AACR
.
Diseases
Validation
Diseases presenting
"tumor growth"
symptom
adrenal incidentaloma
carcinoma of the gallbladder
cholangiocarcinoma
cowden syndrome
cystinuria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
liposarcoma
lymphangioleiomyomatosis
primary effusion lymphoma
severe combined immunodeficiency
von hippel-lindau disease
waldenström macroglobulinemia
wiskott-aldrich syndrome
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