Acta Pharmaceutica Sinica B,
Год журнала:
2024,
Номер
14(7), С. 2815 - 2853
Опубликована: Апрель 24, 2024
Regulated
cell
death
(RCD)
is
a
controlled
form
of
orchestrated
by
one
or
more
cascading
signaling
pathways,
making
it
amenable
to
pharmacological
intervention.
RCD
subroutines
can
be
categorized
as
apoptotic
non-apoptotic
and
play
essential
roles
in
maintaining
homeostasis,
facilitating
development,
modulating
immunity.
Accumulating
evidence
has
recently
revealed
that
evasion
frequently
the
primary
cause
tumor
survival.
Several
have
garnered
attention
promising
cancer
therapies
due
their
ability
induce
regression
prevent
relapse,
comparable
apoptosis.
Moreover,
they
offer
potential
solutions
for
overcoming
acquired
resistance
tumors
toward
drugs.
With
an
increasing
understanding
underlying
mechanisms
governing
these
subroutines,
growing
number
small-molecule
compounds
targeting
single
multiple
pathways
been
discovered,
providing
novel
strategies
current
therapy.
In
this
review,
we
comprehensively
summarized
regulatory
emerging
mainly
including
autophagy-dependent
death,
ferroptosis,
cuproptosis,
disulfidptosis,
necroptosis,
pyroptosis,
alkaliptosis,
oxeiptosis,
parthanatos,
mitochondrial
permeability
transition
(MPT)-driven
necrosis,
entotic
NETotic
lysosome-dependent
immunogenic
(ICD).
Furthermore,
focused
on
discussing
related
compounds.
brief,
insightful
findings
may
provide
valuable
guidance
investigating
individual
collaborative
approaches
towards
different
ultimately
driving
discovery
target
significantly
enhance
future
therapeutics.
Protein & Cell,
Год журнала:
2024,
Номер
15(9), С. 642 - 660
Опубликована: Фев. 29, 2024
Abstract
Cell
death
resistance
represents
a
hallmark
of
cancer.
Recent
studies
have
identified
metabolic
cell
as
unique
forms
regulated
resulting
from
an
imbalance
in
the
cellular
metabolism.
This
review
discusses
mechanisms
death—ferroptosis,
cuproptosis,
disulfidptosis,
lysozincrosis,
and
alkaliptosis—and
explores
their
potential
cancer
therapy.
Our
underscores
complexity
pathways
offers
insights
into
innovative
therapeutic
avenues
for
treatment.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июнь 3, 2024
Abstract
BAX
and
BAK
are
proapoptotic
members
of
the
BCL2
family
that
directly
mediate
mitochondrial
outer
membrane
permeabilition
(MOMP),
a
central
step
in
apoptosis
execution.
However,
molecular
architecture
apoptotic
pore
remains
key
open
question
especially
little
is
known
about
contribution
lipids
to
MOMP.
By
performing
comparative
lipidomics
analysis
proximal
environment
isolated
lipid
nanodiscs,
we
find
significant
enrichment
unsaturated
species
nearby
conditions.
We
then
demonstrate
promote
activity
model
membranes,
mitochondria
cellular
systems,
which
further
supported
by
dynamics
simulations.
Accordingly,
fatty
acid
desaturase
FADS2
not
only
enhances
sensitivity,
but
also
activation
cGAS/STING
pathway
downstream
mtDNA
release.
The
correlation
levels
with
sensitization
different
lung
kidney
cancer
cell
lines
co-treatment
acids
supports
relevance
our
findings.
Altogether,
work
provides
an
insight
on
how
local
affects
function
during
apoptosis.
Cell Death and Disease,
Год журнала:
2024,
Номер
15(11)
Опубликована: Ноя. 26, 2024
Abstract
Regulated
cell
death
(RCD)
refers
to
the
form
of
that
can
be
regulated
by
various
biomacromolecules.
Each
modalities
have
their
distinct
morphological
changes
and
molecular
mechanisms.
However,
intense
evidences
suggest
lipid
peroxidation
common
feature
initiates
propagates
death.
Excessive
alters
property
membrane
further
damage
proteins
nucleic
acids,
which
is
implicated
in
human
pathologies.
Here,
we
firstly
review
classical
chain
process
peroxidation,
clarify
current
understanding
myriad
roles
mechanisms
RCD
types.
We
also
discuss
how
involves
diseases
such
intimate
association
between
peroxidation-driven
leveraged
develop
rational
therapeutic
strategies.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 21, 2025
Abstract
The
B
cell
lymphoma
2
(BCL2)
protein
family
critically
controls
apoptosis
by
regulating
the
release
of
cytochrome
c
from
mitochondria.
In
this
cutting-edge
review,
we
summarize
basic
biology
BCL2
including
canonical
and
non-canonical
functions,
highlight
milestones
research
to
clinical
applications
in
cancer
other
pathophysiological
conditions.
We
review
laboratory
development
BH3-mimetics
as
well
more
recent
approaches
proteolysis
targeting
chimeras
(PROTACs),
antibody-drug
conjugates
(ADCs)
tools
BH4
domain
BCL2.
first
BCL2-selective
BH3-mimetic,
venetoclax,
showed
remarkable
efficacy
with
manageable
toxicities
has
transformed
treatment
several
hematologic
malignancies.
Following
its
success,
chemically
similar
inhibitors
such
sonrotoclax
lisaftoclax
are
currently
under
evaluation,
alone
combination.
Genetic
analysis
highlights
importance
BCL-X
L
MCL1
across
different
types
possible
utility
these
proteins.
However,
or
been
challenging,
on-target
thrombocytopenia
for
cardiac
precluding
development.
Tumor-specific
inhibition
may
be
achieved
novel
using
PROTACs
selective
drug
delivery
strategies
would
transformational
many
subtypes
malignancy.
Taken
together,
envision
that
proteins,
while
already
a
success
story
translational
research,
foreseeable
future
have
broader
applicability
improve
multiple
diseases.
