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Cholangiocarcinoma: molecular pathways and therapeutic opportunities.
[cholangiocarcinoma]
Cholangiocarcinoma
(
CCA
)
is
an
aggressive
biliary
tract
malignancy
with
limited
treatment
options
and
low
survival
rates
.
Currently
,
there
are
no
curative
medical
therapies
for
CCA
.
Recent
advances
have
enhanced
our
understanding
of
the
genetic
basis
of
this
disease
,
and
elucidated
therapeutically
relevant
targets
.
Therapeutic
efforts
in
development
are
directed
at
several
key
pathways
due
to
genetic
aberrations
including
receptor
tyrosine
kinase
pathways
,
mutant
IDH
enzymes
,
the
PI
3
K
-AKT-mTOR
pathway
,
and
chromatin
remodeling
networks
.
A
highly
desmoplastic
,
hypovascular
stroma
is
characteristic
of
CCAs
and
recent
work
has
highlighted
the
importance
of
targeting
this
pathway
via
stromal
myofibroblast
depletion
.
Future
efforts
should
concentrate
on
combination
therapies
with
action
against
the
cancer
cell
and
the
surrounding
tumor
stroma
.
As
the
mutational
landscape
of
CCA
is
being
illuminated
,
molecular
profiling
of
patient
tumors
will
enable
identification
of
specific
mutations
and
the
opportunity
to
offer
directed
,
personalized
treatment
options
.
Diseases
Validation
Diseases presenting
"the opportunity to offer directed"
symptom
cholangiocarcinoma
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