Cancer Cell International,
Journal Year:
2025,
Volume and Issue:
25(1)
Published: Feb. 13, 2025
Abstract
Background
Despite
advancements
in
targeted
therapy
and
immunotherapy,
cutaneous
melanoma
continues
to
have
a
high
mortality
rate
poor
prognosis,
with
therapies
having
limited
efficacy
advanced
melanoma.
Therefore,
it
is
crucial
develop
novel
therapeutics
proven
clinical
potential.
In
this
study,
we
evaluated
the
of
arcyriaflavin
A
(ArcA),
potent
inhibitor
cyclin
D1/CDK4
complex,
suppressing
aggressive
phenotypes
metastatic
Methods
The
effects
ArcA
on
viability
cell
cycle
were
across
four
lines:
WM239A
its
derivatives:
113–6/4L,
131/4-5B1,
131/4-5B2.
Additionally,
performed
wound
healing
transwell
invasion
assays,
followed
by
western
blot.
We
further
established
xenograft
mouse
models
subcutaneously
injecting
them
lines
measured
tumor
size
weight
biweekly.
Immunohistochemistry
analysis
was
compare
protein
expression.
Results
demonstrated
dose-dependent
cytotoxicity,
selectively
targeting
cells
without
affecting
normal
cells,
induced
G
1
arrest.
Moreover,
significantly
inhibited
migration
lines,
accompanied
reduced
expression
levels
p-GSK-3β
(Ser9),
MMP-9,
MMP-13,
suggesting
that
anti-metastatic
may
be
partially
mediated
through
GSK-3β,
MMP-13.
These
findings
validated
using
models;
ArcA-treated
mice
exhibited
smaller
volumes
lighter
weights
compared
vehicle-treated
mice.
confirmed
decreased
p-GSK-3β,
MMP-13
tissues
from
Conclusions
Collectively,
our
indicate
possesses
substantial
anti-tumor
potential,
including
cytotoxic
inhibition
results
suggest
could
enhance
therapeutic
treatment
Cells,
Journal Year:
2021,
Volume and Issue:
10(2), P. 255 - 255
Published: Jan. 28, 2021
Lithium
salts
have
been
in
the
therapeutic
toolbox
for
better
or
worse
since
19th
century,
with
purported
benefit
gout,
hangover,
insomnia,
and
early
suggestions
that
lithium
improved
psychiatric
disorders.
However,
remarkable
effects
of
reported
by
John
Cade
subsequently
Mogens
Schou
revolutionized
treatment
bipolar
disorder.
The
known
molecular
targets
are
surprisingly
few
include
signaling
kinase
glycogen
synthase
kinase-3
(GSK-3),
a
group
structurally
related
phosphomonoesterases
includes
inositol
monophosphatases,
phosphoglucomutase.
Here
we
present
brief
history
uses
then
focus
on
GSK-3
as
target
diverse
diseases,
including
disorder,
cancer,
coronavirus
infections.
Drug Resistance Updates,
Journal Year:
2021,
Volume and Issue:
58, P. 100779 - 100779
Published: Aug. 12, 2021
Pancreatic
cancer
is
an
aggressive
malignancy
with
increasing
incidence
and
poor
prognosis
due
to
its
late
diagnosis
intrinsic
chemoresistance.
Most
pancreatic
patients
present
locally
advanced
or
metastatic
disease
characterized
by
inherent
resistance
chemotherapy.
These
features
pose
a
series
of
therapeutic
challenges
new
targets
are
urgently
needed.
Glycogen
synthase
kinase
3
beta
(GSK3β)
conserved
serine/threonine
kinase,
which
regulates
key
cellular
processes
including
cell
proliferation,
DNA
repair,
cycle
progression,
signaling
metabolic
pathways.
GSK3β
implicated
in
non-malignant
malignant
diseases
inflammation,
neurodegenerative
diseases,
diabetes
cancer.
recently
emerged
among
the
factors
involved
onset
progression
cancer,
as
well
acquisition
Intensive
research
has
been
conducted
on
oncogenic
functions
potential
druggable
target;
currently
developed
inhibitors
display
promising
results
preclinical
models
distinct
tumor
types,
Here,
we
review
latest
findings
about
GSK-3β
biology
role
development
Moreover,
discuss
agents
targeting
that
could
be
administered
monotherapy
combination
other
drugs
surmount
Several
studies
also
defining
gene
signatures
identify
who
might
benefit
from
GSK3β-based
intervention.
This
detailed
overview
emphasizes
urgent
need
additional
molecular
impact
inhibition
structural
analysis
novel
compounds
omics
predictive
biomarkers.
Small,
Journal Year:
2023,
Volume and Issue:
19(16)
Published: Jan. 12, 2023
Abstract
Cancer
metastasis
is
the
major
cause
of
cancer‐related
death.
Excessive
extracellular
matrix
deposition
and
increased
stiffness
are
typical
features
solid
tumors,
creating
confined
spaces
for
tumor
cell
migration
metastasis.
Confined
involved
in
all
steps.
However,
unconfined
inhibitors
different
drugs
available
to
inhibit
rare.
The
main
challenges
modeling
migration,
suffering
low
throughput,
others.
Microfluidic
device
has
advantage
reduce
reagent
consumption
enhance
throughput.
Here,
a
microfluidic
chip
that
can
achieve
multi‐function
drug
screening
against
collective
cancer
cells
under
environment
designed.
This
applied
screen
out
effective
on
among
novel
mechanoreceptors
compound
library
(166
compounds)
hepatocellular
carcinoma,
non‐small
lung
cancer,
breast
pancreatic
ductal
adenocarcinoma
cells.
Three
compounds
significantly
pan‐cancer:
mitochonic
acid
5
(MA‐5),
SB‐705498,
diphenyleneiodonium
chloride
found.
Finally,
it
elucidated
these
targeted
mitochondria,
actin
polymerization,
viability,
respectively.
In
sum,
high‐throughput
platform
targeting
established
three
multiple
types
identified.
Frontiers in Genetics,
Journal Year:
2022,
Volume and Issue:
13
Published: March 8, 2022
Melanoma
is
an
aggressive
malignant
skin
tumour
with
increasing
global
incidence.
However,
current
treatments
have
limitations
owing
to
the
acquired
drug
resistance.
Ferroptosis
a
recently
discovered
form
of
programmed
cell
death
characterised
by
iron
accumulation
and
lipid
peroxidation
plays
critical
role
in
growth
inhibition.
Recently,
ferroptosis
inducers
been
regarded
as
promising
therapeutic
strategy
overcome
apoptosis
resistance
cells.
In
this
study,
we
reported
that
nobiletin,
natural
product
isolated
from
citrus
peel,
exhibited
antitumour
activity
inducing
melanoma
Subsequently,
further
explored
potential
mechanism
nobiletin-induced
ferroptosis,
found
expression
level
glycogen
synthase
kinase
3β
(GSK3β)
tissue
patients
was
significantly
reduced
compared
normal
tissue.
Additionally,
nobiletin
increased
GSK3β
Moreover,
Kelch-like
Ech-associated
protein-1
(Keap1)
increased,
while
nuclear
factor
erythroid
2-related
2
(Nrf2),
haem
oxygenase-1
(HO-1)
decreased
nobiletin-treated
cells,
suggesting
antioxidant
defence
system
downregulated.
Furthermore,
knockdown
upregulated
Keap1/Nrf2/HO-1
signalling
pathway,
opposite
observed
cells
overexpressing
GSK3β.
addition,
molecular
docking
assay
results
indicated
showed
strong
binding
affinities
for
GSK3β,
Keap1,
Nrf2,
HO-1.
Taken
together,
our
demonstrated
could
induce
regulating
GSK3β-mediated
pathway
human
Hence,
stands
candidate
treatment
development
prospects.
BMC Bioinformatics,
Journal Year:
2024,
Volume and Issue:
25(1)
Published: Jan. 22, 2024
Abstract
Background
Driver
genes
play
a
vital
role
in
the
development
of
cancer.
Identifying
driver
is
critical
for
diagnosing
and
understanding
However,
challenges
remain
identifying
personalized
due
to
tumor
heterogeneity
Although
many
computational
methods
have
been
developed
solve
this
problem,
few
efforts
undertaken
explore
gene-patient
associations
identify
genes.
Results
Here
we
propose
method
called
LPDriver
cancer
by
employing
linear
neighborhood
propagation
model
on
individual
genetic
data.
builds
gene
network
based
data
patients,
extracts
from
bipartite
graph
utilizes
mine
detect
The
experimental
results
demonstrate
that
as
compared
existing
methods,
our
shows
competitive
performance
can
predict
more
accurate
way.
Furthermore,
these
also
show
besides
revealing
novel
reported
be
related
with
cancer,
able
patients
their
characteristics
even
if
mutation
are
hidden.
Conclusions
provide
an
effective
approach
genes,
which
could
promote
diagnosis
treatment
source
code
freely
available
at
https://github.com/hyr0771/LPDriver
.
British Journal of Cancer,
Journal Year:
2024,
Volume and Issue:
130(8), P. 1377 - 1387
Published: Feb. 23, 2024
Abstract
Background/objective
To
explore
the
anti-tumour
activity
of
combining
AKT
inhibition
and
docetaxel
in
PTEN
protein
null
WT
prostate
tumours.
Methods
Mechanisms
associated
with
capivasertib
treatment
cancer
were
examined
using
a
panel
vivo
tumour
models
cell
lines.
Results
Combining
had
increased
vivo.
In
vitro
short-term
caused
cycle
arrest
majority
cells.
However,
sub-population
docetaxel-persister
cells
did
not
undergo
G2/M
but
upregulated
phosphorylation
PI3K/AKT
pathway
effectors
GSK3β,
p70S6K,
4E-BP1,
to
lesser
extent
AKT.
acute
induced
p70S6K
4E-BP1
phosphorylation.
Treating
reduced
activation
progression.
it
proliferation
apoptosis
or
DNA
damage
though
effects
more
marked
Docetaxel-persister
partly
reliant
on
GSK3β
as
inhibitor
AZD2858
reversed
capivasertib-induced
damage.
Conclusion
Capivasertib
can
enhance
by
targeting
residual
cells,
independent
status,
induce
part
through
GSK3β.
Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
13
Published: July 14, 2022
Cancer
remains
the
second
leading
cause
of
death
in
US,
accounting
for
25%
all
deaths
nationwide.
Immunotherapy
techniques
bolster
immune
cells'
ability
to
target
malignant
cancer
cells
and
have
brought
immense
improvements
field
treatments.
One
important
inhibitory
protein
T
cells,
programmed
cell
1
(PD-1),
has
become
an
invaluable
immunotherapy.
While
anti-PD-1
antibody
therapy
is
extremely
successful
some
patients,
others
it
fails
or
even
causes
further
complications,
including
hyper-progression
immune-related
adverse
events.
Along
with
countless
translational
studies
PD-1
signaling
pathway,
there
are
currently
close
5,000
clinical
trials
antibodies
against
its
ligand,
PD-L1,
around
80%
which
investigate
combinations
other
therapies.
Nevertheless,
more
work
needed
better
understand
pathway
facilitate
new
improved
evidence-based
combination
strategies.
In
this
work,
we
consolidate
recent
discoveries
mediators
their
therapeutic
potential
anti-PD-1/PD-L1
agents.
We
focus
on
phosphatases
SHP2
PTPN2;
kinases
ITK,
VRK2,
GSK-3,
CDK4/6;
adaptor
PAG.
discuss
biology
both
a
role
relation
determine
combinations.
The
literature
discussed
here
was
obtained
from
search
published
ClinicalTrials.gov
following
key
terms:
checkpoint
inhibition,
immunotherapy,
PD-1,
SHP2,
PTPN2,
CDK4/6,
Together,
find
that
these
proteins
logical
promising
targets
therapy,
deeper
mechanistic
understanding
they
improve
response
rate
decrease
events
when
thoughtfully
used
inhibitors.
European Journal of Pharmaceutical Sciences,
Journal Year:
2022,
Volume and Issue:
180, P. 106323 - 106323
Published: Nov. 4, 2022
In
the
current
investigation,
fifteen
novel
imidazole-pyridine-based
molecules
were
synthesized
and
tested
against
cell
lines
of
lung
(H1299)
colon
(HCT116)
adenocarcinomas
by
proliferation
assay.
The
results
demonstrated
that
compounds
5a,
5d,
5e,
5f
most
active
(IC50<30
µM).
Based
on
recent
literature
results,
glycogen
synthase
kinase-3β
(GSK-3β)
protein
was
investigated
in-silico
as
a
possible
target.
molecular
docking
QSAR
revealed
an
excellent
binding
affinity
selected
imidazole-pyridine
to
GSK-3β.
Notably,
GSK-3β
levels
significantly
upregulated
in
hepatocellular
liver
carcinoma
(LIHCs)
tissues
negatively
affected
patient
prognosis.
Consequently,
evaluated
cancer
(HepG2,
HUH-7,
PLC/PRF/5)
MTT
assay,
5d
showed
highest
antitumor
activity.
This
study
offers
new
with
interesting
biological
activity
target,
exhibiting
potential
therapeutic
impact
for
patients.