Biomolecules,
Год журнала:
2025,
Номер
15(2), С. 248 - 248
Опубликована: Фев. 8, 2025
The
type
I
protein
kinase
PERK
is
an
endoplasmic
reticulum
(ER)
transmembrane
that
plays
a
multifaceted
role
in
cancer
development
and
progression,
influencing
tumor
growth,
metastasis,
cellular
stress
responses.
activation
of
represents
one
the
three
signaling
pathways
induced
during
unfolded
response
(UPR),
which
triggered,
particular,
cells
constitutively
experience
various
intracellular
extracellular
stresses
impair
folding
within
ER.
can
lead
to
both
pro-survival
proapoptotic
outcomes,
depending
on
context
extent
ER
stress.
It
helps
reprogramming
gene
expression
cells,
thereby
ensuring
survival
face
oncogenic
stress,
such
as
replicative
DNA
damage,
also
microenvironmental
challenges,
including
hypoxia,
angiogenesis,
metastasis.
Consequently,
contributes
initiation,
transformation,
adaptation
microenvironment,
chemoresistance.
However,
sustained
cell
proliferation
promote
apoptotic
death
by
interconnected
processes,
mitochondrial
dysfunction,
translational
inhibition,
accumulation
stresses,
specific
induction
multifunctional
factors,
CHOP.
dual
promoting
progression
suppression
makes
it
complex
target
for
therapeutic
interventions.
A
comprehensive
understanding
intricacies
pathway
their
impact
essential
effective
strategies,
particularly
diseases
like
cancer,
where
deregulated
most,
if
not
all,
solid
liquid
tumors.
This
article
provides
overview
knowledge
acquired
from
study
animal
models
lines
cultured
vitro
PERK’s
functions
thus
highlighting
potential
new
avenues
could
this
protein.
Abstract
The
immunological
implications
of
cuproptosis,
a
form
cell
death
highly
sensitive
to
oxygen
presence,
remain
largely
unexplored
in
the
context
tumor
immunotherapy.
Herein,
we
initially
investigate
positive
correlation
between
cuproptosis
and
immunotherapy
through
bioinformatics
analysis.
Subsequently,
an
generator
loaded
with
copper
ions
(
Cu/AP
H‐M)
has
been
constructed,
which
serves
as
effective
carrier
crucially
enhances
oxygenation
microenvironment.
Importantly,
H‐M‐mediated
dual
strengthening
radiotherapy
could
not
only
trigger
powerful
antitumor
immunity
related
immunogenic
by
RNA‐sequencing
analysis,
but
also
effectively
inhibit
growth
both
distal
situ
low
rectal
tumors
after
combined
immunotherapy,
creating
robust
immune
memory
effect.
Our
work
reveals
beneficial
effects
enhanced
radio‐immunotherapy
elucidates
its
underlying
mechanisms,
provides
novel
approach
for
synergistic
integration
radiotherapy,
broadening
scope
cuproptosis‐mediated
therapy.
ACS Nano,
Год журнала:
2023,
Номер
17(21), С. 20875 - 20924
Опубликована: Окт. 23, 2023
Cancer
with
a
complex
pathological
process
is
major
disease
to
human
welfare.
Due
the
imbalance
between
oxygen
(O2)
supply
and
consumption,
hypoxia
natural
characteristic
of
most
solid
tumors
an
important
obstacle
for
cancer
therapy,
which
closely
related
tumor
proliferation,
metastasis,
invasion.
Various
strategies
exploit
feature
have
been
developed
in
past
decade,
can
be
used
alleviate
hypoxia,
or
utilize
targeted
delivery
diagnostic
imaging.
The
include
delivering
O2,
situ
O2
generation,
reprogramming
vascular
system,
decreasing
inhibiting
HIF-1
pathways.
On
other
side,
also
utilized
hypoxia-responsive
chemical
construction
hypoxia-active
prodrug-based
strategies.
Taking
advantage
region,
number
methods
applied
identify
keep
track
changes
hypoxia.
Herein,
we
thoroughly
review
recent
progress
nanomedicine
both
conquering
utilizing
combat
put
forward
prospect
emerging
nanomaterials
future
clinical
transformation,
hopes
provide
perspectives
design.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
176, С. 116783 - 116783
Опубликована: Май 25, 2024
During
tumor
development,
the
itself
must
continuously
generate
new
blood
vessels
to
meet
their
growth
needs
while
also
allowing
for
invasion
and
metastasis.
One
of
most
common
features
tumors
is
hypoxia,
which
drives
process
angiogenesis
by
regulating
microenvironment,
thus
adversely
affecting
prognosis
patients.
In
addition,
overcome
unsuitable
environments
growth,
such
as
nutrient
deficiency,
hyperacidity,
immunosuppression,
microenvironment
(TME)
coordinates
in
several
ways
restore
supply
oxygen
nutrients
remove
metabolic
wastes.
A
growing
body
research
suggests
that
hypoxia
interact
through
a
complex
interplay
crosstalk,
inextricably
linked
TME.
Here,
we
review
TME's
positive
contribution
from
an
angiogenesis-centric
perspective
considering
objective
impact
hypoxic
phenotypes
status
limitations
current
angiogenic
therapies.
Pharmacological Research,
Год журнала:
2025,
Номер
213, С. 107643 - 107643
Опубликована: Фев. 4, 2025
Glutamine
metabolism
is
emerging
as
a
target
for
improving
immunotherapy
efficacy.
However,
the
outcomes
remain
inconclusive.
Given
that
tumor-intrinsic
response
to
interferon-γ
(IFN-γ)
key
determinant
of
efficacy,
we
investigated
whether
and
how
glutamine
deprivation
in
cancer
cells
affects
their
IFN-γ.
By
using
human
lung
cell
lines,
patient-derived
tumor
explants,
syngeneic
mouse
model
cancer,
demonstrated
reduced
IFN-γ-driven
by
promoting
autophagy-dependent
IFN-γ
receptor
(IFNGR1)
degradation
rendering
tumors
resistant
anti-PD-1
or
anti-PD-L1
therapy.
Treatment
with
V9302,
an
inhibitor
alanine-serine-cysteine
transporter
(ASCT2),
enhanced
increased
efficacy
PD-1
blockade
Mechanistic
analysis
revealed
V9302
inhibited
autophagy
impairing
lysosomal
activity
independent
deprivation,
likely
because
its
physiochemical
properties,
thereby
preventing
IFNGR1
degradation.
Moreover,
also
Glut1
expression
through
inhibition
pathway-dependent
consequently
glucose
uptake,
turn
retaining
levels
intracellular
alpha-ketoglutarate
(α-KG)
ATP,
which
are
involved
maintaining
signal
transduction
cells.
In
support
these
findings,
targeting
chloroquine
(CQ)
The
administration
CQ
sensitivity
ASCT2-deficient
per
se
leads
resistance
immunotherapy,
whereas
treatment
results
impaired
activity,
deprivation.
