Journal of Personalized Medicine,
Journal Year:
2022,
Volume and Issue:
12(8), P. 1247 - 1247
Published: July 29, 2022
Recent
years
have
witnessed
the
advent
of
molecular
profiling
for
intrahepatic
cholangiocarcinoma
(iCCA),
and
new
techniques
led
to
identification
several
alterations.
Precision
oncology
approaches
been
widely
evaluated
are
currently
under
assessment,
as
shown
by
recent
development
a
wide
range
agents
targeting
Fibroblast
Growth
Factor
Receptor
(FGFR)
2,
Isocitrate
Dehydrogenase
1
(IDH-1),
BRAF.
However,
knowledge
gaps
persist
in
understanding
genomic
landscape
this
hepatobiliary
malignancy.In
current
study,
we
aimed
comprehensively
analyze
clinicopathological
features
BAP1-mutated
iCCA
patients
public
datasets
increase
on
biological
profile
iCCA.The
database
including
772
iCCAs,
identified
BAP1
mutations
120
cases
(15.7%).
According
our
analysis,
no
differences
terms
overall
survival
relapse-free
were
observed
between
wild-type
receiving
radical
surgery.
In
addition,
IDH1,
PBRM1,
ARID1A
most
commonly
co-altered
genes
iCCAs.The
characterization
is
destined
become
increasingly
important,
more
efforts
implement
genomics
analysis
warranted.
Signal Transduction and Targeted Therapy,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: April 13, 2025
Oncogenic
gene
fusions
occur
across
a
broad
range
of
cancers
and
are
defining
feature
some
cancer
types.
Cancers
driven
by
fusion
products
tend
to
respond
well
targeted
therapies,
where
available;
thus,
detection
potentially
targetable
oncogenic
is
necessary
select
optimal
treatment.
Detection
methods
include
non-sequencing
methods,
such
as
fluorescence
in
situ
hybridization
immunohistochemistry,
sequencing
DNA-
RNA-based
next-generation
(NGS).
While
NGS
an
efficient
way
analyze
multiple
genes
interest
at
once,
economic
technical
factors
may
preclude
its
use
routine
care
globally,
despite
several
guideline
recommendations.
The
aim
this
review
present
summary
fusions,
with
focus
on
that
affect
tyrosine
kinase
signaling,
highlight
the
importance
testing
for
fusions.
We
overview
identification
therapies
approved
treatment
harboring
summarize
data
regarding
treating
fusion-positive
no
current
clinical
studies
cancers.
Although
options
be
limited
patients
rare
alterations,
healthcare
professionals
should
identify
most
likely
benefit
from
initiate
appropriate
therapy
achieve
outcomes.
Expert Opinion on Drug Safety,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 8
Published: May 1, 2025
Futibatinib
is
a
small,
potent,
covalent,
irreversible
fibroblast
growth
factor
receptor
(FGFR)
1-4
inhibitor
that
has
been
added
as
new
standard
of
care
for
previously
treated
unresectable
and/or
advanced
FGFR2
fusion/rearrangement-positive
BTC.
fusions/rearrangements
play
key
role
in
BTC
survival,
proliferation,
invasion,
and
development
distant
metastasis.
The
inhibition
this
pathway
an
important
target
the
treatment
article
covers
futibatinib
refractory
unresectable/advanced
BTC,
its
mechanism
action,
pharmacodynamic/pharmacokinetic
data
with
focus
on
safety
profile.
Data
are
based
published
clinical
trials,
pooled
analysis,
retrospective
studies
indexed
PubMed
(2010-2024).
FDA
EMA
approved
patients
fusions/rearrangements.
Ongoing
drug
strategies
centered
designing
fusion
inhibitors
able
to
overcome
on-target
off-target
resistances
coupled
high
selectivity
spare
most
common
treatment-related
adverse
events
(hyperphosphatemia,
stomatitis,
alopecia,
nail
toxicity,
skin
reactions,
eye
toxicity).
ABSTRACT
The
tumour
microenvironment
(TME)
significantly
influences
formation
and
progression
through
dynamic
interactions.
Cholangiocarcinoma
(CCA),
a
highly
desmoplastic
tumour,
lacks
early
diagnostic
biomarkers
has
limited
effective
treatments
owing
to
incomplete
understanding
of
its
molecular
pathogenesis.
Investigating
the
role
TME
in
CCA
could
lead
better
therapies.
RNA
sequencing
was
performed
on
seven
patient-derived
xenografts
(PDXs)
their
corresponding
patient
samples.
Differential
expression
analysis
conducted,
Qiagen
Ingenuity
Pathway
Analysis
used
predict
dysregulated
pathways
upstream
regulators.
PDX-
cell
line-derived
spheroids,
with
without
immortalised
mesenchymal
stem
cells,
were
grown
analysed
for
morphology,
growth
viability.
Histological
confirmed
biliary
phenotypes.
indicated
upregulation
extracellular
matrix-receptor
interaction
PI3K-AKT
presence
several
genes
linked
poor
survival.
Mesenchymal
cells
restored
activity
inhibited
cancer-associated
kinases.
Thus,
adding
spheroid
models
key
paracrine
signalling
lost
PDXs,
enhancing
These
findings
highlight
importance
including
stromal
components
cancer
improve
pre-clinical
studies.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(16), P. 2889 - 2889
Published: Aug. 20, 2024
Intrahepatic
cholangiocarcinoma
(iCCA)
is
recognized
worldwide
as
the
second
leading
cause
of
morbidity
and
mortality
among
primary
liver
cancers,
showing
a
continuously
increasing
incidence
rate
in
recent
years.
iCCA
aggressiveness
revealed
through
its
rapid
silent
intrahepatic
expansion
spread
lymphatic
system
to
late
diagnosis
poor
prognoses.
Multi-omics
studies
have
aggregated
information
derived
from
single-omics
data,
providing
more
comprehensive
understanding
phenomena
being
studied.
These
approaches
are
gradually
becoming
powerful
tools
for
investigating
intricate
pathobiology
iCCA,
facilitating
correlation
between
molecular
signature
phenotypic
manifestation.
Consequently,
preliminary
stratifications
patients
been
proposed
according
their
"omics"
features
opening
possibility
identifying
potential
biomarkers
early
developing
new
therapies
based
on
personalized
medicine
(PM).
The
focus
this
review
provide
advanced
insight
into
starting
single-
latest
multi-omics
approaches,
paving
way
translating
basic
research
therapeutic
practices.
Technology in Cancer Research & Treatment,
Journal Year:
2023,
Volume and Issue:
22
Published: Jan. 1, 2023
Cholangiocarcinomas
(CCAs)
are
a
group
of
heterogeneous
epithelial
malignancies
that
can
originate
at
the
level
any
location
biliary
tree.
These
tumors
relatively
rare
but
associated
with
high
rate
mortality.
CCAs
morphologically
and
molecularly
for
their
be
distinguished
as
intracellular
extracellular,
subdivided
into
perihilar
distal.
Recent
epidemiological,
molecular,
cellular
studies
have
supported
consistent
heterogeneity
observed
may
result
from
convergence
various
key
elements
mainly
represented
by
risk
factors,
molecular
abnormalities
genetic
epigenetic
levels
different
potential
cells
origin.
consistently
contributed
to
better
defining
pathogenesis
identify
in
some
instances
new
therapeutic
targets.
Although
progress
were
still
limited,
these
observations
suggest
understanding
mechanisms
underlying
CCA
future
will
help
develop
more
efficacious
treatment
strategies.
Open Life Sciences,
Journal Year:
2023,
Volume and Issue:
18(1)
Published: Jan. 1, 2023
Abstract
The
aim
of
this
study
is
to
investigate
certain
genetic
features
intrahepatic
cholangiocarcinoma
(ICCA).
A
total
12
eligible
ICCA
patients
were
enrolled,
and
tumor
tissues
from
the
subjected
next-generation
sequencing
a
multi-genes
panel.
Tumor
mutation
burden
(TMB),
mutated
genes,
copy
number
variants
(CNVs),
pathway
enrichment
analysis
performed.
median
TMB
was
2.76
Mutation/Mb
(range,
0–36.62
Mutation/Mb)
in
patients.
top
two
most
commonly
genes
KRAS
(33%)
TP53
(25%).
co-mutations
16.7%
(2/12)
Notably,
patient
P6
with
highest
did
not
have
mutations.
Additionally,
and/or
alterations
significantly
associated
poor
progression-free
survival
than
those
wild
type
(1.4
months
vs
18
months).
DNA
damage
repair
homologs
recombinant
deficiencies
high
cases.
In
conclusion,
we
found
that
mutations
could
predict
prognosis
