Cancer Cell,
Год журнала:
2024,
Номер
42(5), С. 850 - 868.e9
Опубликована: Апрель 25, 2024
TP53-mutant
blood
cancers
remain
a
clinical
challenge.
BH3-mimetic
drugs
inhibit
BCL-2
pro-survival
proteins,
inducing
cancer
cell
apoptosis.
Despite
acting
downstream
of
p53,
functional
p53
is
required
for
maximal
killing
by
BH3-mimetics
through
an
unknown
mechanism.
Here,
we
report
activated
following
induced
mitochondrial
outer
membrane
permeabilization,
leading
to
BH3-only
protein
induction
and
thereby
potentiating
the
pro-apoptotic
signal.
TP53-deficient
lymphomas
lack
this
feedforward
loop,
providing
opportunities
survival
disease
relapse
after
treatment.
The
therapeutic
barrier
imposed
defects
in
TP53
can
be
overcome
direct
activation
cGAS/STING
pathway,
which
promotes
apoptosis
cells
p53-independent
upregulation.
Combining
clinically
relevant
STING
agonists
with
efficiently
kills
TRP53/TP53-mutant
mouse
B
lymphoma,
human
NK/T
acute
myeloid
leukemia
cells.
This
represents
promising
therapy
regime
that
fast-tracked
tackle
clinic.
Cell Death and Disease,
Год журнала:
2023,
Номер
14(10)
Опубликована: Окт. 20, 2023
Abstract
Atherosclerosis
is
a
chronic
inflammatory
disease
characterized
by
the
accumulation
of
fatty
deposits
in
inner
walls
vessels.
These
plaques
restrict
blood
flow
and
lead
to
complications
such
as
heart
attack
or
stroke.
The
development
atherosclerosis
influenced
variety
factors,
including
age,
genetics,
lifestyle,
underlying
health
conditions
high
pressure
diabetes.
Atherosclerotic
stable
form
are
slow
growth,
which
leads
luminal
stenosis,
with
low
embolic
potential
unstable
form,
contributes
risk
for
thrombotic
rapid
clinical
onset.
In
this
complex
scenario
atherosclerosis,
macrophages
participate
whole
process,
initiation,
growth
eventually
rupture
wound
healing
stages
artery
plaque
formation.
Macrophages
exhibit
heterogeneity
plasticity,
affect
evolving
microenvironment,
e.g.,
leading
excessive
lipid
accumulation,
cytokine
hyperactivation,
hypoxia,
apoptosis
necroptosis.
metabolic
functional
transitions
response
microenvironmental
factors
not
only
influence
ongoing
imminent
responses
within
lesions
but
also
directly
dictate
atherosclerotic
progression
regression.
review,
we
discuss
origin
plaques,
their
phenotypic
diversity,
shifts,
fate
roles
they
play
dynamic
atherosclerosis.
It
describes
how
interact
other
cells,
particularly
T
cells.
Ultimately,
targeting
pathways
involved
macrophage
polarization
may
innovative
promising
approaches
precision
medicine.
Further
insights
into
landscape
biological
features
offer
valuable
information
optimizing
future
treatment
macrophages.
Autophagy,
Год журнала:
2024,
Номер
20(6), С. 1213 - 1246
Опубликована: Март 6, 2024
Macroautophagy/autophagy
is
a
complex
degradation
process
with
dual
role
in
cell
death
that
influenced
by
the
types
are
involved
and
stressors
they
exposed
to.
Ferroptosis
an
iron-dependent
oxidative
form
of
characterized
unrestricted
lipid
peroxidation
context
heterogeneous
plastic
mechanisms.
Recent
studies
have
shed
light
on
involvement
specific
autophagy
(e.g.
ferritinophagy,
lipophagy,
clockophagy)
initiating
or
executing
ferroptotic
through
selective
anti-injury
proteins
organelles.
Conversely,
other
forms
reticulophagy
lysophagy)
enhance
cellular
defense
against
damage.
Dysregulated
autophagy-dependent
ferroptosis
has
implications
for
diverse
range
pathological
conditions.
This
review
aims
to
present
updated
definition
ferroptosis,
discuss
influential
substrates
receptors,
outline
experimental
methods,
propose
guidelines
interpreting
results.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Янв. 24, 2024
Abstract
Ferroptosis
represents
a
distinct
form
of
programmed
cell
death
triggered
by
excessive
iron
accumulation
and
lipid
peroxidation-induced
damage.
This
mode
differentiates
from
classical
in
terms
morphology
biochemistry.
stands
out
for
its
exceptional
biological
characteristics
has
garnered
extensive
research
conversations
as
death.
Its
dysfunctional
activation
is
closely
linked
to
the
onset
diseases,
particularly
inflammation
cancer,
making
ferroptosis
promising
avenue
combating
these
conditions.
As
such,
exploring
may
offer
innovative
approaches
treating
cancer
inflammatory
diseases.
Our
review
provides
insights
into
relevant
regulatory
mechanisms
ferroptosis,
examining
impact
ferroptosis-related
factors
both
physiological
pathological
perspectives.
Describing
crosstalk
between
tumor-
inflammation-associated
signaling
pathways
potential
inducers
overcoming
drug-resistant
cancers
are
discussed,
aiming
inform
further
novel
therapeutic
directions
relation
Immunological Reviews,
Год журнала:
2023,
Номер
321(1), С. 115 - 127
Опубликована: Сен. 4, 2023
Type
I
interferon
(IFN)
is
a
class
of
proinflammatory
cytokines
with
dual
role
on
malignant
transformation,
tumor
progression,
and
response
to
therapy.
On
the
one
hand,
robust,
acute,
resolving
type
IFN
responses
have
been
shown
mediate
prominent
anticancer
effects,
reflecting
not
only
their
direct
cytostatic/cytotoxic
activity
(at
least
some)
cells,
but
also
pronounced
immunostimulatory
functions.
In
line
this
notion,
signaling
has
implicated
in
antineoplastic
effects
various
immunogenic
therapeutics,
including
(but
limited
to)
cell
death
(ICD)-inducing
agents
immune
checkpoint
inhibitors
(ICIs).
other
weak,
indolent,
non-resolving
demonstrated
support
progression
resistance
therapy,
ability
suboptimal
cytoprotective
activity,
promote
stemness,
favor
tolerance
chromosomal
instability,
facilitate
establishment
an
immunologically
exhausted
microenvironment.
Here,
we
review
fundamental
aspects
context-dependent
impact
