Background:
Triple-negative
breast
cancer
(TNBC)
is
a
highly
aggressive
subtype
with
limited
effective
treatments
available,
including
targeted
therapies,
often
leading
to
poor
prognosis.
Mitotic
checkpoint
kinase
BUB1
frequently
overexpressed
in
TNBC
and
correlates
survival
outcomes
suggesting
its
potential
as
therapeutic
target.
This
study
explores
the
cytotoxicity
of
cells
inhibition,
alone
or
combination
radiation
demonstrates
that
ferroptosis,
an
iron-dependent
form
programmed
cell
death,
has
role.
Methods:
lines
(SUM159,
MDA-MB-231,
BT-549)
were
treated
inhibitor
BAY1816032
(BUB1i)
ferroptosis
activator
RSL3
without
4
Gy
irradiation.
Cell
viability
assays
conducted
assess
treatment
effects,
qPCR
analyses
measured
expression
key
markers
ACSL4,
GPX4,
PTGS2,
SLC7A11,
NCOA4,
IREB2,
NFS1,
TFRC
expression,
TBARS
assay
lipid
peroxidation
levels.
Ferroptosis
specificity
was
confirmed
through
co-treatment
Ferrostatin-1
(F-1).
Results:
In
all
studied,
inhibition
significantly
induced
marked
by
increased
ACSL4
decreased
GPX4
The
BUB1i
further
amplified
these
ferroptotic
markers,
at
least
additive
effect,
which
not
present
radiation.
Co-treatment
reversed
BUB1i-mediated
death
may
involve
signaling
lines.
Conclusions:
independently
induce
lines,
enhanced
when
combined
activator.
Further
research
warranted
delineate
molecular
mechanism
BUB1-mediated
TNBC.
Journal of Hematology & Oncology,
Год журнала:
2025,
Номер
18(1)
Опубликована: Янв. 13, 2025
The
tumor
microenvironment
(TME)
is
integral
to
cancer
progression,
impacting
metastasis
and
treatment
response.
It
consists
of
diverse
cell
types,
extracellular
matrix
components,
signaling
molecules
that
interact
promote
growth
therapeutic
resistance.
Elucidating
the
intricate
interactions
between
cells
TME
crucial
in
understanding
progression
challenges.
A
critical
process
induced
by
epithelial-mesenchymal
transition
(EMT),
wherein
epithelial
acquire
mesenchymal
traits,
which
enhance
their
motility
invasiveness
progression.
By
targeting
various
components
TME,
novel
investigational
strategies
aim
disrupt
TME's
contribution
EMT,
thereby
improving
efficacy,
addressing
resistance,
offering
a
nuanced
approach
therapy.
This
review
scrutinizes
key
players
emphasizing
avenues
therapeutically
components.
Moreover,
article
discusses
implications
for
resistance
mechanisms
highlights
current
toward
modulation
along
with
potential
caveats.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Фев. 18, 2025
Abstract
Breast
cancer,
characterized
by
unique
epidemiological
patterns
and
significant
heterogeneity,
remains
one
of
the
leading
causes
malignancy-related
deaths
in
women.
The
increasingly
nuanced
molecular
subtypes
breast
cancer
have
enhanced
comprehension
precision
treatment
this
disease.
mechanisms
tumorigenesis
progression
been
central
to
scientific
research,
with
investigations
spanning
various
perspectives
such
as
tumor
stemness,
intra-tumoral
microbiota,
circadian
rhythms.
Technological
advancements,
particularly
those
integrated
artificial
intelligence,
significantly
improved
accuracy
detection
diagnosis.
emergence
novel
therapeutic
concepts
drugs
represents
a
paradigm
shift
towards
personalized
medicine.
Evidence
suggests
that
optimal
diagnosis
models
tailored
individual
patient
risk
expected
are
crucial,
supporting
era
oncology
for
cancer.
Despite
rapid
advancements
increasing
emphasis
on
clinical
comprehensive
update
summary
panoramic
knowledge
related
disease
needed.
In
review,
we
provide
thorough
overview
global
status
including
its
epidemiology,
factors,
pathophysiology,
subtyping.
Additionally,
elaborate
latest
research
into
contributing
progression,
emerging
strategies,
long-term
management.
This
review
offers
valuable
insights
Cancer
Research,
thereby
facilitating
future
progress
both
basic
application.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(14), С. 7544 - 7544
Опубликована: Июль 9, 2024
Ferroptosis
is
a
type
of
nonapoptotic
cell
death
that
characteristically
caused
by
phospholipid
peroxidation
promoted
radical
reactions
involving
iron.
Researchers
have
identified
many
the
protein
factors
are
encoded
genes
promote
ferroptosis.
Glutathione
peroxidase
4
(GPX4)
key
enzyme
protects
phospholipids
from
and
suppresses
ferroptosis
in
glutathione-dependent
manner.
Thus,
dysregulation
involved
cysteine
and/or
glutathione
metabolism
closely
associated
with
From
perspective
dynamics,
actively
proliferating
cells
more
prone
to
than
quiescent
cells,
which
suggests
species
generated
during
oxygen-involved
responsible
for
lipid
peroxidation.
Herein,
we
discuss
initial
events
dominantly
occur
process
energy
metabolism,
association
deficiency.
Accordingly,
tricarboxylic
acid
cycle
coupled
respiratory
chain
mitochondria
main
subjects
here,
this
likely
source
both
electrons
free
Since
not
only
carbohydrates,
but
also
amino
acids,
especially
glutamate,
major
substrates
central
dealing
nitrogen
derived
groups
contributes
subject
discussion.
The
gut
microbiota
can
produce
a
variety
of
microbial-derived
metabolites
to
influence
tumor
development.
Tryptophan,
an
essential
amino
acid
in
the
human
body,
be
converted
by
microorganisms
via
indole
pathway
such
as
Indole-3-Lactic
Acid
(ILA),
Indole-3-Propionic
(IPA),
Indole
Acetic
(IAA)
and
Indole-3-Aldehyde
(IAld).
Recent
studies
have
shown
that
play
key
roles
progression,
they
used
adjuvant
regimens
for
immunotherapy
or
chemotherapy.
Here,
we
summarize
recent
findings
on
common
microbial
provide
review
mechanisms
different
microenvironment.
We
further
discuss
limitations
current
metabolite
research
future
possibilities.
It
is
expected
will
new
strategies
clinical
therapy.
Ferroptosis
is
a
nonapoptotic
form
of
cell
death
characterized
by
iron-dependent
lipid
peroxidation
in
membrane
phospholipids.
Since
its
identification
2012,
extensive
research
has
unveiled
involvement
the
pathophysiology
numerous
diseases,
including
cancers,
neurodegenerative
disorders,
organ
injuries,
infectious
autoimmune
conditions,
metabolic
and
skin
diseases.
Oxidizable
lipids,
overload
iron,
compromised
antioxidant
systems
are
known
as
critical
prerequisites
for
driving
overwhelming
peroxidation,
ultimately
leading
to
plasma
rupture
ferroptotic
death.
However,
precise
regulatory
networks
governing
ferroptosis
ferroptosis-targeted
therapy
these
diseases
remain
largely
undefined,
hindering
development
pharmacological
agonists
antagonists.
In
this
review,
we
first
elucidate
core
mechanisms
summarize
epigenetic
modifications
(e.g.,
histone
modifications,
DNA
methylation,
noncoding
RNAs,
N6-methyladenosine
modification)
nonepigenetic
genetic
mutations,
transcriptional
regulation,
posttranslational
modifications).
We
then
discuss
association
between
disease
pathogenesis
explore
therapeutic
approaches
targeting
ferroptosis.
also
introduce
potential
clinical
monitoring
strategies
Finally,
put
forward
several
unresolved
issues
which
progress
needed
better
understand
hope
review
will
offer
promise
application
therapies
context
human
health
disease.
DNAJC15
is
a
mitochondrial
TIMM23-related
co-chaperonin
known
for
its
role
in
regulating
oxidative
phosphorylation
efficiency,
stress
response
and
lipid
metabolism.
Recently,
it
has
been
proposed
that
the
loss
of
correlates
with
cisplatin
(CDDP)-resistance
onset
ovarian
cancer
(OC),
suggesting
this
protein
as
potential
prognostic
factor
during
OC
progression.
However,
molecular
mechanisms
through
which
contributes
to
CDDP
remains
poorly
investigated.
Here,
we
show
high
levels
are
associated
accumulation
droplets,
decreased
tumorigenic
features
increased
sensitivity
cells.
When
overexpressed,
induced
phenotype
displaying
peroxidation
subsequent
ferroptosis
induction.
To
prove
DNAJC15-induced
promoting
CDDP,
reduced
upon
Ferrostatin
1
treatment,
cells'
vulnerability
ultimately
recovering
their
CDDP-resistant
phenotype.
In
conclusion,
our
study
uncovers
modulating
activation
resistance
Advanced Functional Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 19, 2025
Abstract
Ferroptosis
is
a
newly
identified
type
of
regulated
cell
death
characterized
by
iron‐dependent
lipid
peroxidation.
Among
the
main
ferroptosis‐suppressing
systems,
dihydroorotate
dehydrogenase
(DHODH)‐
ubiquinone
axis
closely
related
to
mitochondria
and
energy
metabolism,
implying
that
protects
cells
from
oxidative
stress
damage
via
maintenance
redox
homeostasis.
However,
ferroptosis
initiation
requires
suitable
environment
breakthrough
in
homeostatic
limitations
systems.
Hence,
nanoparticles
are
rationally
engineered
achieve
efficient
induction
releasing
dual‐release
free
iron
disrupting
Atovaquone
(ATO)‐loaded
hollow
mesoporous
etching
zeolitic
imidazolate
framework‐67
double‐coated
oxide/calcium
phosphate
(Fe
3
O
4
/CaP)
conjugated
with
polyethylene
glycol.
The
external
Fe
/CaP
structure
enhances
efficiency
multiple
reactive
oxygen
species
(ROS)
generation
promoting
stress.
Still,
it
achieves
increase
content
unstable
pools
for
igniting
ROS
storm
peroxidation
spark.
release
ATO
not
only
affects
metabolism
mitochondrial
respiratory
chain
binding
complex
III
but
also
downregulates
DHODH
restrict
ubiquinol
system
disrupt
Therefore,
design
this
composite
nanomedicine
provides
an
approach
inducing
theoretical
basis
clinical
anti‐tumor
trials.
