ONCOLOGIE,
Год журнала:
2024,
Номер
26(5), С. 783 - 797
Опубликована: Июль 29, 2024
Abstract
Objectives
Cuproptosis
represents
the
copper-dependent
novel
cell
death
pattern.
However,
effects
of
cuproptosis-related
sorafenib-resistant
genes
on
prognosis,
treatment
response,
and
sorafenib
resistance
in
hepatocellular
carcinoma
(HCC)
patients
are
still
unclear.
The
present
work
aims
to
develop
a
signature
for
predicting
HCC
prognosis.
Methods
Cuproptosis-related
differentially
expressed
(CRSRDEGs)
were
identified
by
correlation
analysis
between
cuproptosis
using
electronic
databases
TCGA
GEO.
Besides,
risk
score
model
(CRSRRSM)
was
established
through
LASSO
univariate
Cox
regression
analyses.
Later,
this
adopted
analyzing
patient
Certain
potential
drugs
sensitivity
also
analyzed
receiving
or
transarterial
chemoembolization
(TACE)
treatment.
Results
CRSRRSM
achieved
excellent
efficiency
prognosis
TACE
response
patients.
As
revealed
somatic
mutational
analyses,
associated
with
tumor
burden
(TMB),
especially
TP53,
CSMD3,
OBSCN
mutations.
According
functional
enrichment
analysis,
closely
correlated
tumor-related
pathways,
tricarboxylic
acid
(TCA)
cycle,
drug
resistance.
Notably,
such
as
sepantronium
bromide,
AZD8055,
RO-3306,
promising
alternatives
treating
resistance,
proposed
based
CRSRRSM.
Furthermore,
single-cell
transcriptomic
that
high-risk
malignant
cells
demonstrated
an
increased
capacity
proliferation
immune
evasion.
Conclusions
A
model,
designated
CRSRRSM,
constructed
can
effectively
predict
This
provides
implications
clinical
management
Asian Journal of Pharmaceutical Sciences,
Год журнала:
2025,
Номер
unknown, С. 101020 - 101020
Опубликована: Янв. 1, 2025
Immunotherapy
with
interleukin-2
(IL-2)
in
treating
cancers
is
subject
to
several
limitations
such
as
systemic
side
effects
and
reduced
efficacy
against
tumors
low
immune
cell
infiltration
despite
its
promise.
To
address
these
challenges,
IL-2-So-Lipo,
a
novel
liposomal
formulation
combining
IL-2
sorafenib
derivative,
was
developed
an
anti-angiogenic
drug
that
inhibits
the
growth
of
new
blood
vessels
which
play
crucial
roles
tumor
growth.
Sorafenib
derivatives
could
target
at
melanoma-specific
receptors,
further
enhancing
specificity
site.
Our
results
demonstrated
prepared
IL-2-So-Lipo
significantly
enhanced
anti-tumor
activity
compared
or
monotherapies,
well
their
combination.
In
B16F10
melanoma
model,
found
inhibit
progression
(tumor
volume
108.01
±
62.99
mm3)
control
group
1,397.13
75.55
mm3),
improving
therapeutic
efficacy.
This
attributed
targeted
delivery
promoted
activation
cytotoxic
T
lymphocytes.
Additionally,
encapsulation
efficiency,
promoting
apoptosis
suppressing
angiogenesis.
Mechanistically,
kill
by
inducing
shift
towards
response
via
facilitating
polarization
macrophages
M1
phenotype.
Furthermore,
downregulated
key
proteins
MAPK
signaling
pathway,
exerting
significant
role
mediating
resistance
sorafenib.
These
findings
underscore
potential
promising
strategy
improve
immunotherapy
therapy
cancers.
Moreover,
combination
system
overcame
conventional
therapy,
offering
synergistic
approach
outcomes
for
solid
tumors.
Hepatoma Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 23, 2025
Hepatocellular
carcinoma
(HCC)
represents
a
significant
global
health
challenge,
with
complex
etiology
and
limited
treatment
options.
The
integration
of
multi-omics
technologies,
including
genomics,
transcriptomics,
proteomics,
metabolomics,
has
revolutionized
our
understanding
HCC,
offering
novel
insights
into
its
molecular
underpinnings.
This
comprehensive
review
synthesizes
the
current
knowledge
on
application
in
highlighting
role
disease
classification,
early
detection,
development
targeted
therapies.
We
discuss
identification
key
driver
mutations
single
nucleotide
polymorphisms
(SNPs)
that
enhance
risk
prediction
models,
implications
for
personalized
medicine.
approach
facilitated
discovery
distinct
HCC
subtypes,
each
unique
signatures
tumor
microenvironments
(TME),
which
are
critical
predicting
prognosis
guiding
strategies.
Furthermore,
we
explore
these
findings
precision
medicine,
emphasizing
potential
biomarker
therapies,
immune
checkpoint
blockade
(ICB).
concludes
by
underscoring
transformative
impact
research
clinical
practice,
heralding
new
era
medicine
promise
improved
patient
outcomes.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 17, 2025
Hepatocellular
carcinoma
(HCC)
is
the
most
prevalent
primary
liver
malignancy
and
a
leading
cause
of
cancer-related
deaths
globally.
The
asymptomatic
progression
early-stage
HCC
often
results
in
diagnosis
at
advanced
stages,
significantly
limiting
therapeutic
options
worsening
prognosis.
Immunotherapy,
with
immune
checkpoint
inhibitors
(ICIs)
forefront,
has
revolutionized
treatment.
Nevertheless,
tumor
heterogeneity,
evasion,
presence
immunosuppressive
components
within
microenvironment
(TIME)
continue
to
compromise
its
efficacy.
Furthermore,
resistance
or
non-responsiveness
ICIs
some
patients
underscores
urgent
need
unravel
complexities
TIME
design
innovative
strategies
that
enhance
immunotherapeutic
outcomes.
Emerging
evidence
revealed
pivotal
role
N6-methyladenosine
(m6A),
prominent
RNA
methylation
modification,
shaping
HCC.
By
regulating
stability
translation,
m6A
influences
immune-related
factors,
including
cytokines
molecules.
This
modification
governs
PD-L1
expression,
facilitating
escape
contributing
against
ICIs.
Advances
this
field
have
also
identified
m6A-related
regulators
as
promising
biomarkers
for
predicting
immunotherapy
response
potential
targets
optimizing
treatment
review
examines
regulatory
mechanisms
HCC,
focus
on
impact
cells
cytokine
dynamics.
It
explores
targeting
pathways
improve
efficacy
outlines
emerging
directions
future
research.
These
insights
aim
provide
foundation
developing
novel
overcome
advance
Molecular Pharmaceutics,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 23, 2025
Integrin
αvβ3
expression
is
associated
with
sorafenib
resistance
in
hepatocellular
carcinoma
(HCC).
Therefore,
monitoring
its
HCC
may
serve
as
a
valuable
indicator
of
the
efficacy
treatment.
In
this
study,
longitudinal
positron
emission
tomography
(PET)
was
performed
to
assess
[18F]Alfatide
II
and
[18F]fluorodeoxyglucose
([18F]FDG)
suitable
probes
for
evaluating
treatment
Huh-7
human
(HCC)
xenograft
model.
tumor
cells
were
used
establish
both
normal
sorafenib-resistant
cell
lines,
models
developed.
The
mice
categorized
into
four
groups
based
on
type
treatment:
nontreatment,
treatment,
received
intragastric
injections
(30
mg/kg/day)
or
vehicle
15
consecutive
days.
Tumor
size
weight
assessed
throughout
study.
Longitudinal
microPET/computed
(CT)
scans
[18F]FDG
acquired
quantitatively
measure
angiogenesis
days
-2,
3,
7,
14
metabolism
-1,
4,
8,
following
therapy
initiation.
uptake
(ID%/gmean)
each
probe
calculated.
No
significant
difference
observed
between
(P
=
0.452);
however,
differed
significantly
two
<
0.001).
Sorafenib
successfully
inhibited
growth,
inducing
differences
9
after
0.05).
lesions
changed
day
However,
no
change
>
PET
imaging
data
validated
through
ex
vivo
immunohistochemistry
analysis
targeting
integrin
αvβ3,
VEGF,
GULT-1.
more
effective
therapeutic
model
than
[18F]FDG.
Pharmaceuticals,
Год журнала:
2025,
Номер
18(4), С. 492 - 492
Опубликована: Март 28, 2025
Tyrosine
kinase
inhibitors
(TKIs)
have
revolutionized
cancer
treatments
by
being
less
toxic
and
improving
the
survival
of
patients.
The
greatest
challenge
to
their
success
is
resistance
exhibited
However,
potential
microRNAs
(miRNAs)
for
sensitizing
molecules
TKIs
has
been
well
recognized,
with
several
reports
publishing
promising
results.
Nonetheless,
this
therapeutic
window
faces
challenges
often-overlooked
limitations.
One
most
fundamental
selecting
optimal
miRNA
candidates
clinical
trials,
as
miRNAs
are
promiscuous
regulate
hundreds
targets.
In
review,
we
describe
how
enhance
sensitivity
across
various
types
cancer.
We
highlight
limitations
in
achieving
a
successful
collaboration
between
small
(TKIs–miRNAs).
Our
focus
on
proposing
workflow
select
suitable
candidate,
recommending
available
bioinformatics
tools
develop
partnership
miRNAs.
hope
that
initial
proposal
will
provide
valuable
support
future
research.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(8), С. 3491 - 3491
Опубликована: Апрель 8, 2025
Hepatocellular
carcinoma
(HCC)
is
a
lethal
malignancy
associated
with
drug
resistance,
resulting
in
poor
prognosis.
High
mobility
group
box
1
(HMGB1)
chromatin-binding
protein
that
regulates
HCC
progression.
The
overexpression
of
HMGB1
has
been
found
to
promote
tumorigenesis
and
resistance.
In
this
study,
we
aimed
investigate
the
role
expression
metastasis
its
impact
on
sorafenib
oxaliplatin
Tissue
samples
from
patients
(n
=
48)
were
subjected
immunohistochemistry.
was
correlated
clinical
pathology
parameters.
Moreover,
cell
line
HuH-7
used
study
regulatory
effect
proliferation,
adhesion,
migration,
invasion
by
using
siRNA
(small
interfering
RNA)
silencing
method.
Furthermore,
challenges
performed
determine
sensitivity
chemotherapeutic
drugs
(sorafenib
oxaliplatin).
significantly
overexpressed
tumor
tissues,
highlighted
increment
M1
advanced
tumors
immunoreactivity
scores
2.61
6.50
for
adjacent
respectively
(p-values
0.0035).
involved
mechanisms
then
described
through
suppression
silencing.
Notably,
inhibition
promoted
sorafenib/oxaliplatin
increasing
toxicity
about
13-18%.
Our
demonstrated
shows
potential
as
promising
biomarker
target
treatment
tumorigenesis,
metastasis,
chemo-drug