Notch signaling pathway in cancer: from mechanistic insights to targeted therapies
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Май 27, 2024
Notch
signaling,
renowned
for
its
role
in
regulating
cell
fate,
organ
development,
and
tissue
homeostasis
across
metazoans,
is
highly
conserved
throughout
evolution.
The
receptor
ligands
are
transmembrane
proteins
containing
epidermal
growth
factor-like
repeat
sequences,
typically
necessitating
receptor-ligand
interaction
to
initiate
classical
signaling
transduction.
Accumulating
evidence
indicates
that
the
pathway
serves
as
both
an
oncogenic
factor
a
tumor
suppressor
various
cancer
types.
Dysregulation
of
this
promotes
epithelial-mesenchymal
transition
angiogenesis
malignancies,
closely
linked
proliferation,
invasion,
metastasis.
Furthermore,
contributes
maintaining
stem-like
properties
cells,
thereby
enhancing
invasiveness.
regulatory
metabolic
reprogramming
microenvironment
suggests
pivotal
involvement
balancing
suppressive
effects.
Moreover,
implicated
conferring
chemoresistance
cells.
Therefore,
comprehensive
understanding
these
biological
processes
crucial
developing
innovative
therapeutic
strategies
targeting
signaling.
This
review
focuses
on
research
progress
cancers,
providing
in-depth
insights
into
potential
mechanisms
regulation
occurrence
progression
cancer.
Additionally,
summarizes
pharmaceutical
clinical
trials
therapy,
aiming
offer
new
human
malignancies.
Язык: Английский
Notch signaling in the tumor immune microenvironment of colorectal cancer: mechanisms and therapeutic opportunities
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Март 12, 2025
Colorectal
cancer
(CRC)
remains
a
leading
cause
of
cancer-related
morbidity
and
mortality
worldwide,
driven
by
complex
interplay
genetic,
environmental,
immune-related
factors.
Among
the
pivotal
pathways
implicated
in
CRC
tumorigenesis,
Notch
signaling
pathway
is
instrumental
governing
cell
fate
decisions,
tissue
renewal,
homeostasis,
immune
development.
As
highly
conserved
mechanism,
not
only
modulates
tumor
behavior
but
also
shapes
landscape
within
microenvironment
(TME).
Aberrant
fosters
evasion
progression
through
its
effects
on
balance
functionality
cells,
including
myeloid-derived
suppressor
cells
(MDSCs)
tumor-associated
macrophages
(TAMs).
Elevated
activation
correlates
with
advanced
clinicopathological
features
poorer
clinical
outcomes,
highlighting
relevance
as
both
prognostic
biomarker
therapeutic
target.
Therapeutic
approaches
aimed
at
inhibiting
pathway,
such
γ-secretase
inhibitors
(GSIs)
or
monoclonal
antibodies
(mAbs)
combination
other
therapies,
have
demonstrated
promising
efficacy
preclinical
settings.
This
review
examines
impact
immunity,
elucidating
regulatory
mechanisms
role
promoting
progression.
Additionally,
this
discusses
strategies
targeting
signaling,
GSIs,
mAbs,
potential
therapies
designed
to
overcome
resistance
improve
patient
outcomes.
By
multifaceted
TME,
underscores
target
for
innovative
strategies.
Язык: Английский
Kinsenoside‐Loaded Microneedle Accelerates Diabetic Wound Healing by Reprogramming Macrophage Metabolism via Inhibiting IRE1α/XBP1 Signaling Axis
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 25, 2025
Abstract
Continuously
bacterial
infection,
undue
oxidative
stress,
and
inflammatory
responses
in
the
skin
tissue
microenvironment
determine
delayed
healing
outcome
of
diabetic
wounds,
which
remain
a
tough
clinical
challenge
need
multifaceted
therapeutic
strategies.
In
this
work,
HA‐ADH/HA‐QA‐ALD‐based
hydrogel
microneedle
(HAQA‐MN)
with
antimicrobial
antioxidative
activities
incorporating
kinsenoside
(KD)
coated
macrophage
membrane
(M‐KD)
targeting
inflammation
relief
is
developed
to
improve
cutaneous
micro‐niche.
KD
observed
trigger
trimethylamine
N‐oxide‐irritated
proinflammatory
macrophages
repolarization
from
M1
state
anti‐inflammatory
M2
phenotype,
underlying
mechanism
due
drug‐induced
IRE1α/XBP1/HIF‐1α
pathway
suppression,
accompanied
by
diminution
glycolysis
enhancement
phosphorylation,
resulting
cascade
inhibition
signaling
enhancement.
The
hydrazone
cross‐linked
HAQA‐MN
possesses
favorable
biocompatibility,
self‐healing,
controlled
release
M‐KD
excellent
mechanical
properties.
Moreover,
MN
patch
remarkedly
restrains
survival
E.
coli
S.
aureus
eliminates
hydrogen
peroxide
preserve
cellular
viability.
Notably,
M‐KD@HAQA‐MN
array
effectively
ameliorates
stress
facilitate
angiogenesis
collagen
deposition,
thereby
accelerating
regeneration
mice
full‐thickness
defect
model.
Collectively,
study
highlights
multifunctional
platform
as
promising
candidate
application
for
treatment
wounds.
Язык: Английский
Engineering synthetic agonists for targeted activation of Notch signaling
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 6, 2024
ABSTRACT
Notch
signaling
regulates
cell
fate
decisions
and
has
context-dependent
tumorigenic
or
tumor
suppressor
functions.
Although
there
are
several
classes
of
inhibitors,
the
mechanical
force
requirement
for
receptor
activation
hindered
attempts
to
generate
soluble
agonists.
To
address
this
problem,
we
engineered
synthetic
agonist
(SNAG)
proteins
by
tethering
affinity-matured
ligands
antibodies
cytokines
that
internalize
their
targets.
This
bispecific
format
enables
SNAGs
“pull”
on
mechanosensitive
receptors,
triggering
in
presence
a
desired
biomarker.
We
successfully
developed
targeting
six
independent
surface
markers,
including
antigens
PDL1,
CD19,
HER2,
immunostimulatory
CD40.
CD40
increase
expansion
central
memory
γδ
T
cells
from
peripheral
blood,
highlighting
potential
improve
phenotype
yield
low-abundance
subsets.
These
insights
have
broad
implications
pharmacological
mechanoreceptors
will
expand
our
ability
modulate
biotechnology.
Язык: Английский
Notch signaling in digestive system cancers: Roles and therapeutic prospects
Cellular Signalling,
Год журнала:
2024,
Номер
unknown, С. 111476 - 111476
Опубликована: Окт. 1, 2024
Язык: Английский
Promising therapeutic targets for tumor treatment: Cleaved activation of receptors in the nucleus
Drug Discovery Today,
Год журнала:
2024,
Номер
unknown, С. 104192 - 104192
Опубликована: Сен. 1, 2024
Язык: Английский
A comprehensive review of oncogenic Notch signaling in multiple myeloma
PeerJ,
Год журнала:
2024,
Номер
12, С. e18485 - e18485
Опубликована: Ноя. 28, 2024
Multiple
myeloma
remains
an
incurable
plasma
cell
cancer
with
radical
case-by-case
heterogeneity.
Because
of
this,
personalized
and
disease-specific
biology
multiple
must
be
understood
for
the
discovery
effective
molecular
targets.
The
highly
evolutionarily
conserved
Notch
signaling
pathway
has
been
extensively
described
as
a
multifaceted
driver
disease
process—contributing
to
both
intrinsic
effects
malignant
cells
widespread
remodeling
tumor
microenvironment
that
further
facilitates
progression.
Namely,
amongst
promotes
increased
proliferation,
tumor-initiating
capacity,
drug
resistance,
invasiveness.
Moreover,
between
leads
osteodegenerative
angiogenesis.
This
comprehensive
review
will
discuss
implications
pathological
in
extrinsic
microenvironment.
Additionally,
genetic
origins
dysregulation
current
attempts
at
targeting
therapeutically
reviewed.
While
subject
reviewed
previously,
recent
developments
intervening
years
demand
revised
synthesis
literature.
aim
this
work
is
introduce
thoroughly
synthesize
state
knowledge
vein
research
highlight
future
directions
new
in-the-field
scientists.
Язык: Английский