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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
.