Safety profile of EZH2 inhibitors for cancer: a systematic review and meta-analysis
PeerJ,
Год журнала:
2025,
Номер
13, С. e18871 - e18871
Опубликована: Янв. 27, 2025
To
evaluate
the
safety
profiles
of
EZH2-targeted
inhibitors
in
cancer
treatment,
focusing
on
treatment-related
adverse
events
(TRAEs)
across
various
clinical
trials.
We
conducted
a
systematic
review
and
meta-analysis
using
data
from
trials
involving
EZH2
reported
up
to
May
31,
2024.
Databases
searched
included
PubMed,
Embase,
CENTRAL
(Cochrane
Central
Register
Controlled
Trials),
ClinicalTrials.gov.
Studies
were
those
patients
treated
with
as
monotherapy
or
combination,
specifically
detailing
incidence
TRAEs.
Data
all-grade
TRAEs,
grade
3
higher
severe
TRAEs
extracted
analyzed
random-effects
models.
Our
22
studies
encompassing
1,002
who
met
inclusion
criteria.
commonly
observed
during
inhibitor
therapy,
affecting
86%
(95%
CI
[79-94%]%;
I2
=
89.5%).
The
was
33%
[21-44%];
93.5%),
while
occurred
15%
cases
[9-22%];
87.5%).
most
frequently
pooled
analysis
neutropenia
(8%),
thrombocytopenia
anemia
(6%).
Specifically,
for
tazemetostat,
common
TRAE
(5%).
For
SHR2554,
prevalent
(17%),
(7%).
Notably,
fatalities
rare,
only
0.9%
experiencing
potentially
fatal
outcomes
due
therapy.
demonstrate
manageable
profile
low
emphasizing
their
potential
safe
therapeutic
options
treatment.
rate
rare
occurrences
deaths
support
continued
use
further
investigation
inhibitors.
Язык: Английский
Immunohistochemical Profiling of Histone Modification Biomarkers Identifies Subtype-Specific Epigenetic Signatures and Potential Drug Targets in Breast Cancer
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(2), С. 770 - 770
Опубликована: Янв. 17, 2025
Breast
cancer
(BC)
subtypes
exhibit
distinct
epigenetic
landscapes,
with
triple-negative
breast
(TNBC)
lacking
effective
targeted
therapies.
This
study
investigates
histone
biomarkers
and
therapeutic
vulnerabilities
across
BC
subtypes.
The
immunohistochemical
profiling
of
>20
biomarkers,
including
modifications,
modifiers,
oncohistone
mutations,
was
conducted
on
a
discovery
cohort
validation
tissues,
healthy
controls,
cell
line
models.
Transcriptomic
growth
analyses
were
to
evaluate
the
effects
small-molecule
G9a
inhibitor
in
diverse
Key
H3K9me2,
H3K36me2,
H3K79me,
differentially
expressed
H3K9me2
emerged
as
an
independent
predictor
for
distinguishing
TNBC
from
other
less-aggressive
subtypes,
elevated
expression
correlating
higher
tumor
grade
stage.
inhibition
impaired
proliferation
modulated
epithelial–mesenchymal
transition
pathways,
strongest
impact
basal-like
TNBC.
disruption
oncogene
suppressor
regulation
(e.g.,
TP53,
SATB1)
observed
highlights
G9a’s
context-dependent
roles
BC,
supporting
its
potential
target.
findings
provide
foundation
subtype-specific
therapies
improve
outcomes
aggressive
Язык: Английский
A narrative review of epigenetic marker in H3K27ac and its emerging potential as a therapeutic target in cancer
Epigenomics,
Год журнала:
2025,
Номер
unknown, С. 1 - 17
Опубликована: Фев. 21, 2025
Histone
acetylation,
particularly
H3
K27
acetylation
(H3K27ac),
is
a
critical
post-translational
modification
that
regulates
chromatin
structure
and
gene
expression,
which
plays
significant
role
in
various
cancers,
including
breast,
colon,
lung,
hepatocellular,
prostate
cancer.
However,
the
mechanisms
of
H3K27ac
tumorigenesis
are
not
yet
comprehensive,
especially
its
epigenetic
mechanisms.
This
review
endeavors
to
discuss
findings
on
involvement
carcinogenesis
within
past
5
years
through
literature
search
using
academic
databases
such
as
Web
Science.
Firstly,
we
provide
an
overview
diverse
landscape
histone
modifications,
emphasizing
distinctive
characteristics
significance
H3K27ac.
Secondly,
summarize
compare
advanced
high-throughput
sequencing
technologies
have
been
utilized
construction
map.
Thirdly,
elucidate
mediating
transcription.
Fourthly,
venture
into
potential
molecular
mechanism
cancer
development.
Finally,
engage
discussing
future
therapeutic
approaches
oncology,
with
spotlight
strategies
harness
H3K27
modifications.
In
conclusion,
this
comprehensively
summarizes
underscores
pivotal
cancer,
providing
valuable
insights
target
for
intervention.
Язык: Английский
Exploring Mechanisms of Action in Combinatorial Therapy through Stability/Solubility Alterations: Advancing AML Treatment
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 8, 2024
Abstract
Acute
myeloid
leukemia
(AML)
is
an
aggressive
blood
cancer
with
a
poor
prognosis.
Although
treatments
like
allogeneic
hematopoietic
stem
cell
transplantation
and
high-dose
chemotherapy
can
potentially
cure
younger
patients
in
some
cases,
challenges
such
as
relapse
treatment-related
toxicities
remain
significant.
Combination
therapy
has
been
cornerstone
AML
treatment,
offering
enhanced
efficacy
by
leveraging
the
synergistic
effects
of
multiple
agents.
However,
high
toxicity
levels
genetic
heterogeneity
complicate
identification
effective
universally
applicable
drug
regimens.
To
address
these
challenges,
we
introduce
CoPISA
workflow
(Proteome
Integral
Solubility/Stability
Alteration
Analysis
for
Combinations),
innovative
method
designed
to
study
drug-target
interactions
specifically
within
combination
therapies.
detects
changes
protein
solubility/stability
that
occur
only
when
two
drugs
are
used
together,
revealing
cooperative
mechanisms
single-drug
cannot
achieve.
We
applied
this
highly
low-toxicity
combinations
AML,
previously
introduced
our
group:
LY3009120-sapanisertib
(LS)
ruxolitinib-ulixertinib
(RU).
utilizes
advanced
proteomic
tools
investigate
both
primary
secondary
target
effects,
providing
deeper
understanding
how
therapies
influence
signaling
pathways
overcome
resistance.
Furthermore,
propose
novel
concept
termed
“conjunctional
inhibition”,
where
combined
action
induces
biological
responses
be
achieved
individual
This
approach
introduces
transformation
designing
combinatorial
offers
new
directions
more
other
complex
diseases.
Язык: Английский
Immunohistochemical Profiling of Histone Modification Biomarkers Identifies Subtype-Specific Epigenetic Signatures and Potential Drug Targets in Breast Cancer
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 17, 2024
Abstract
Background:
Breast
cancer
(BC)
subtypes
exhibit
distinct
epigenetic
landscapes,
with
triple-negative
breast
(TNBC)
lacking
effective
targeted
therapies.
This
study
investigates
histone
biomarkers
and
therapeutic
vulnerabilities
across
BC
subtypes.
Methods:
Immunohistochemical
profiling
of
>20
biomarkers,
including
modifications,
modifiers
oncohistone
mutations
was
conducted
on
a
discovery
cohort
validation
tissues,
healthy
controls
cell
line
models.
Transcriptomic
growth
analyses
were
to
evaluate
the
effects
small-molecule
G9a
inhibitor
in
diverse
Results:
Key
H3K9me2,
H3K36me2,
H3K79me,
differentially
expressed
H3K9me2
emerged
as
an
independent
predictor
for
distinguishing
TNBC
from
other
less
aggressive
subtypes,
elevated
expression
correlating
higher
tumor
grade
stage.
inhibition
impaired
proliferation
modulated
epithelial-mesenchymal
transition
pathways,
strongest
impact
basal-like
TNBC.
Disruption
oncogene
suppressor
regulation
(e.g.,
TP53,
SATB1)
observed
Conclusion:
highlights
G9a’s
context-dependent
roles
BC,
supporting
its
potential
target.
Findings
provide
foundation
subtype-specific
therapies
improve
outcomes
Clinical
Perspective
undertaken
explore
landscape
focusing
modifications
their
potential,
particularly
through
targeting
G9a,
methyltransferase.
The
identified
emerging
key
marker
demonstrated
robust
anti-cancer
effects,
impairment
disruption
oncogenic
These
findings
compelling
evidence
development
similar
regulators,
highlighting
reshape
treatment
patient
outcomes.
Язык: Английский