bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 5, 2023
Abstract
In
the
continuous
pursuit
of
advanced
cancer
therapeutics,
our
research
unveils
potential
to
selectively
target
Voltage-Dependent
Anion-selective
Channel
isoform
1
(VDAC1),
a
pivotal
component
in
cellular
metabolism
and
apoptosis.
VDAC1’s
role
metabolic
rewiring
its
subsequent
prominence
many
types
offer
unique
intervention
point.
The
incorporation
systematic,
silico
vitro
methodology
identified
novel
VA
(
V
DAC-
A
ntagonist)
molecules
with
capability
bind
VDAC1,
displaying
substantial
specificity
towards
cells
while
sparing
healthy
ones.
This
first
led
revelation
specialized
VDAC1
pocket,
which
accommodates
binding
these
molecules,
thereby
instigating
selective
displacement
NADH.
coenzyme
is
critical
substrate,
ensues
notable
mitochondrial
distress
reduction
cell
proliferation,
specifically
cells.
Furthermore,
meticulous
analysis
using
organoids
derived
from
intrahepatic
cholangiocarcinoma
patients
(iCCA)
demonstrated
dose-dependent
viability
upon
treatment
correlating
findings
commercial
lines.
Interestingly,
significantly
reduced
lower
impact
on
than
conventional
treatments
like
gemcitabine.
differential
possibly
due
elevated
expression
various
lines,
rendering
them
more
susceptible
disruptions
induced
by
molecules.
endeavor
uncovers
multifaceted
approach
treatment,
involving
targeting
gatekeepers
entities,
paving
way
for
developing
refined
therapeutics.
albeit
nascent
stages,
represent
promising
candidates
further
optimization
development,
potentially
revolutionizing
modalities
therapy
through
precise
interventions.
iLiver,
Journal Year:
2024,
Volume and Issue:
3(1), P. 100083 - 100083
Published: Feb. 9, 2024
Hepatocellular
carcinoma
(HCC)
is
a
prevalent
malignancy
worldwide,
ranking
as
the
sixth
most
common
and
third
leading
cause
of
cancer-related
mortality.
Late
diagnosis,
limited
management
options,
its
complex
etiology
contribute
to
poor
prognosis
high
mortality
rates.
Recent
advances
in
understanding
molecular
mechanisms
HCC
innovations
high-throughput
sequencing
technologies
have
led
development
diagnostics
personalized
therapies
for
this
challenging
malignancy.
This
review
provides
comprehensive
overview
research
on
diagnosis
individualized
treatment
HCC.
We
highlight
key
potential
future
directions
discuss
application
next-generation
identify
characterize
genetic
epigenetic
alterations
patients.
These
may
aid
selection
targeted
therapies,
prediction
response,
monitoring
disease
progression.
Furthermore,
we
explore
role
liquid
biopsy
prediction,
monitoring,
focusing
circulating
tumor
cells,
DNA,
extracellular
vesicles.
also
evolving
landscape
therapy
HCC,
including
against
oncogenic
signaling
pathways,
immune
checkpoint
inhibitors,
tumor-agnostic
innovative
cell-based
therapies.
challenges
opportunities
that
lie
ahead
quest
improve
patient
outcomes
through
integration
precision
emphasize
need
multi-interdisciplinary
collaboration,
refinement
predictive
prognostic
biomarkers,
more
effective
combination
strategies
new
area
medicine.
Expert Opinion on Drug Discovery,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 22, 2025
Biliary
tract
cancer
(BTC)
comprises
a
clinically
diverse
and
genetically
heterogeneous
group
of
tumors
along
the
intra-
extrahepatic
biliary
system
(intrahepatic
cholangiocarcinoma)
gallbladder
with
common
feature
poor
prognosis,
despite
increasing
molecular
knowledge
associated
genetic
aberrations
possible
targeted
therapies.
Therefore,
search
for
even
more
precise
individualized
therapies
is
ongoing
preclinical
tumor
models
are
central
to
development
such
new
approaches.
The
described
in
current
review
include
simple
advanced
vitro
vivo
models,
including
cell
lines,
2D
monolayer,
spheroid
organoid
cultures,
3D
bioprinting,
patient-derived
xenografts,
recently,
machine-perfusion
platform-based
resected
liver
specimens.
All
these
have
individual
advantages,
disadvantages
limitations
that
need
be
considered
depending
on
desired
application.
In
addition
potential
cost
limitations,
availability
BTC
types,
time
required
model
establishment
growth
success
rate,
differently
reflect
relevant
characteristics
as
heterogeneity,
spatial
tumor-stroma
microenvironment
interactions,
metabolic
nutritional
gradients
immunological
interactions.
consequent
combination
different
may
improve
clinical
study
outcomes
by
strengthening
data
basis.
iScience,
Journal Year:
2024,
Volume and Issue:
27(6), P. 109853 - 109853
Published: April 30, 2024
The
voltage-dependent
anion-selective
channel
isoform
1
(VDAC1)
is
a
pivotal
component
in
cellular
metabolism
and
apoptosis
with
prominent
role
many
cancer
types,
offering
unique
therapeutic
intervention
point.
Through
an
Biochemical Pharmacology,
Journal Year:
2023,
Volume and Issue:
217, P. 115803 - 115803
Published: Sept. 12, 2023
Breast
cancer
stands
as
the
most
prevalent
and
heterogeneous
malignancy
affecting
women
globally,
posing
a
substantial
health
concern.
Enhanced
comprehension
of
tumor
pathology
development
novel
therapeutics
are
pivotal
for
advancing
breast
treatment.
Contemporary
investigation
heavily
leans
on
in
vivo
models
conventional
cell
culture
techniques.
Nonetheless,
these
approaches
often
encounter
high
failure
rates
clinical
trials
due
to
species
disparities
tissue
structure
variations.
To
address
this,
three-dimensional
cultivation
organoids,
resembling
organ-like
structures,
has
emerged
promising
alternative.
Organoids
represent
innovative
vitro
that
mirror
microenvironments.
They
retain
original
tumor's
diversity
facilitate
expansion
samples
from
diverse
origins,
facilitating
representation
varying
stages.
Optimized
organoid
models,
under
precise
conditions,
offer
benefits
including
convenient
sample
acquisition,
abbreviated
durations,
genetic
stability.
These
attributes
ensure
faithful
replication
traits
cells.
As
intricate
cellular
entities
boasting
spatial
arrangements,
harbor
potential
precision
medicine,
organ
transplantation,
modeling
diseases,
gene
therapy,
drug
innovation.
This
review
delivers
an
overview
techniques
outlines
future
prospects
modeling.
Pathogens,
Journal Year:
2023,
Volume and Issue:
12(7), P. 940 - 940
Published: July 15, 2023
It
is
estimated
that
25%
of
the
world's
population
has
non-alcoholic
fatty
liver
disease.
This
disease
can
advance
to
a
more
severe
form,
steatohepatitis
(NASH),
with
greater
probability
progression
cirrhosis
and
hepatocellular
carcinoma
(HCC).
NASH
could
be
characterized
as
necro-inflammatory
complication
chronic
hepatic
steatosis.
The
combination
factors
lead
its
HCC
in
setting
inflammation
not
clearly
understood.
portal
vein
main
route
communication
between
intestine
liver.
allows
transfer
products
derived
from
response
pathway
bile
antibody
secretion
intestine.
intestinal
microbiota
performs
fundamental
role
regulation
immune
function,
but
it
undergo
changes
alter
functionality.
These
also
contribute
cancer
by
disrupting
system
causing
dysfunction,
both
which
are
implicated
development.
In
this
article,
we
address
link
inflammation,
HCC.
We
review
different
vitro
models,
well
recent
clinical
trials
addressing
microbiota.
Discover Oncology,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: April 10, 2025
Abstract
Hepatocellular
carcinoma
(HCC),
with
high
incidence
and
mortality
rates
among
digestive
system
diseases,
has
become
a
focal
point
for
researchers.
However,
the
more
we
learn
about
HCC,
apparent
it
becomes
that
our
understanding
is
still
superficial.
The
successes
failures
of
numerous
studies
underscore
urgent
need
precision
medicine
in
cancer
treatment.
A
crucial
aspect
preclinical
research
experimental
model,
particularly
cell
culture
models.
Among
these,
3D
models
can
effectively
integrate
simulate
tumor
microenvironment,
closely
reflecting
vivo
conditions
patients.
This
capability
provides
solid
theoretical
foundation
personalized
treatment
approaches.
In
this
review,
first
outline
common
vitro
examine
essential
elements
within
followed
by
insights
into
current
state
future
developments
HCC.
