Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Src Mutation Induces Acquired Lapatinib Resistance in ERBB2-Amplified Human Gastroesophageal Adenocarcinoma Models.
[esophageal adenocarcinoma]
ERBB
2
-
directed
therapy
is
now
a
routine
component
of
therapy
for
ERBB
2
-
amplified
metastatic
gastroesophageal
adenocarcinomas
.
However
,
there
is
little
knowledge
of
the
mechanisms
by
which
these
tumors
develop
acquired
resistance
to
ERBB
2
inhibition
.
To
investigate
this
question
we
sought
to
characterize
cell
line
models
of
ERBB
2
-
amplified
gastroesophageal
adenocarcinoma
with
acquired
resistance
to
ERBB
2
inhibition
.
We
generated
lapatinib-resistant
(
LR
)
subclones
from
an
initially
lapatinib-sensitive
ERBB
2
-
amplified
esophageal
adenocarcinoma
cell
line
,
OE
19
.
We
subsequently
performed
genomic
characterization
and
functional
analyses
of
resistant
subclones
with
acquired
lapatinib
resistance
.
We
identified
a
novel
,
acquired
SrcE
527
K
mutation
in
a
subset
of
LR
OE
19
subclones
.
Cells
with
this
mutant
allele
harbour
increased
Src
phosphorylation
.
Genetic
and
pharmacologic
inhibition
of
Src
resensitized
these
subclones
to
lapatinib
.
Biochemically
,
Src
mutations
could
activate
both
the
phosphatidylinositol
3
-
kinase
and
mitogen
activated
protein
kinase
pathways
in
the
lapatinib-treated
LR
OE
19
cells
.
Ectopic
expression
of
Src
E
527
K
mutation
also
was
sufficient
to
induce
lapatinib
resistance
in
drug-naïve
cells
.
These
results
indicate
that
pathologic
activation
of
Src
is
a
potential
mechanism
of
acquired
resistance
to
ERBB
2
inhibition
in
ERBB
2
-
amplified
gastroesophageal
cancer
.
Although
Src
mutation
has
not
been
described
in
primary
tumor
samples
,
we
propose
that
the
Src
hyperactivation
should
be
investigated
in
the
settings
of
acquired
resistance
to
ERBB
2
inhibition
in
esophageal
and
gastric
adenocarcinoma
.
Diseases
Validation
Diseases presenting
"tumor samples"
symptom
carcinoma of the gallbladder
cutaneous mastocytosis
dedifferentiated liposarcoma
esophageal adenocarcinoma
esophageal squamous cell carcinoma
pleomorphic liposarcoma
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom