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Antitumor effects and molecular mechanisms of figitumumab, a humanized monoclonal antibody to IGF-1 receptor, in esophageal carcinoma.
[esophageal squamous cell carcinoma]
The
insulin
-like
growth
factor
type
1
receptor
(
IGF-
1
R
)
plays
an
essential
role
in
the
development
of
numerous
cancers
.
Figitumumab
(
CP
)
is
not
only
a
monocloncal
antibody
,
it
also
has
agonist
activity
on
IGF-
1
R
.
The
antitumor
activity
of
CP
in
esophageal
squamous
cell
carcinoma
(
ESCC
)
is
still
unclear
.
In
our
study
,
we
identified
IGF-
1
R
as
an
independent
prognostic
factor
in
ESCC
patients
,
and
investigated
the
antitumor
effects
of
CP
in
ESCC
cell
lines
.
CP
suppressed
tumor
growth
and
sensitized
cells
to
chemotherapeutic
drugs
.
In
addition
,
CP
inhibited
cell
proliferation
,
migration
,
colony
forming
activity
and
anti-apoptosis
induced
by
IGF-
1
.
Our
results
showed
that
CP
not
only
inhibited
IGF-
1
induced
receptor
autophosphorylation
and
downstream
signaling
,
but
also
triggered
β-arrestin
1
and
G
protein-coupled
receptor
kinases
(
GRKs
)
mediated
ERK
1
/
2
activation
,
indicating
CP
as
a
biased
agonist
for
IGF-
1
R
.
Inhibition
of
ERK
1
/
2
enhanced
the
antitumor
activity
of
CP
.
Furthermore
,
CP
was
a
more
powerful
agonist
for
IGF-
1
R
down-regulation
than
IGF-
1
,
and
dysregulation
of
β-arrestin
1
and
GRKs
affected
this
down-regulation
.
Thus
,
we
demonstrated
antitumor
activities
of
CP
on
ESCC
,
and
as
a
biased
agonist
,
CP
induced
ERK
1
/
2
activation
and
receptor
down-regulation
required
β-arrestin
1
and
GRKs
,
suggesting
a
promising
role
for
targeting
IGF-
1
R
in
ESCC
.
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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