Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 22, 2024
Abstract
Triple
negative
breast
cancer
(TNBC)
subtype
is
characterized
with
higher
EMT/stemness
properties
and
immune
suppressive
tumor
microenvironment
(TME).
Women
advanced
TNBC
exhibit
aggressive
disease
have
limited
treatment
options.
Although
TME
implicated
in
driving
of
basal/TNBC
therapy
resistance,
effectively
targeting
it
remains
a
challenge.
Minnelide,
prodrug
triptolide
currently
being
tested
clinical
trials,
has
shown
anti-tumorigenic
activity
multiple
malignancies
via
super
enhancers,
Myc
anti-apoptotic
pathways
such
as
HSP70.
Distinct
super-enhancer
landscape
drives
stem
cells
(CSC)
while
inducing
TME.
We
show
that
Minnelide
selectively
targets
CSCs
human
murine
cell
lines
compared
to
luminal
by
combination
cyclophosphamide
significantly
reduces
the
growth
eliminates
metastasis
reprogramming
enhancing
cytotoxic
T
infiltration
4T1
tumor-bearing
mice.
Resection
residual
tumors
following
leads
complete
eradication
disseminated
all
mice
are
free
local
distant
recurrences.
All
control
showed
recurrences
within
3
weeks
post-resection
single
delayed
recurrence
one
mouse
was
tumor.
provide
evidence
intrinsic
reprograms
microenvironment.
Our
studies
also
suggest
may
lead
durable
responses
patients
warranting
its
investigation.
Clinical and Translational Science,
Journal Year:
2023,
Volume and Issue:
16(8), P. 1331 - 1339
Published: April 21, 2023
NUT
midline
carcinoma
family
member
1
(NUTM1)
fusions
were
originally
identified
in
poorly
differentiated
and
clinically
aggressive
carcinomas
typically
located
the
structures
of
children
young
adults,
collectively
known
as
(midline)
carcinomas.
Next-generation
sequencing
later
uncovered
NUTM1
a
variety
other
pediatric
adult
cancers
diverse
location
type,
including
hematologic
malignancies,
cutaneous
adnexal
tumors,
sarcomas.
A
vast
array
with
bromodomain
containing
4
(BRD4)
or
3
(BRD3),
which
are
characteristic
carcinoma,
several
fusion
partners
have
been
associated
variable
prognosis.
These
non-kinase
thought
to
cause
epigenetic
reprogramming,
thereby
promoting
proliferation,
hindering
differentiation
cancer
cells.
Many
questions
about
both
function
naïve
protein,
is
mostly
restricted
germ
cells
testis
related
spermatogenesis
oncogenic
mechanisms
various
cancer,
still
unanswered.
Moreover,
whether
there
relationship
defined
by
presence
between
conventional
NUTM1-rearranged
neoplasms
remains
be
elucidated.
This
review
will
focus
on
recent
discoveries
found
cancers,
their
prognostic
impact,
emergence
novel
drivers.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(23), P. 17085 - 17085
Published: Dec. 3, 2023
Neuroblastoma
(NB),
a
childhood
cancer
arising
from
the
neural
crest,
poses
significant
clinical
challenges,
particularly
in
cases
featuring
amplification
of
MYCN
oncogene.
Epigenetic
factors
play
pivotal
role
normal
crest
and
NB
development,
influencing
gene
expression
patterns
critical
for
tumorigenesis.
This
review
delves
into
multifaceted
interplay
between
known
epigenetic
modifications
during
genesis,
shedding
light
on
intricate
regulatory
networks
underlying
disease.
We
provide
an
extensive
survey
mechanisms,
encompassing
DNA
methylation,
histone
modifications,
non-coding
RNAs,
super-enhancers
(SEs),
bromodomains
(BET),
chromatin
modifiers
MYCN-amplified
(MNA)
NB.
These
changes
collectively
contribute
to
dysregulated
landscape
observed
MNA
Furthermore,
we
emerging
therapeutic
strategies
targeting
regulators,
including
deacetylase
inhibitors
(HDACi),
methyltransferase
(HMTi),
(DNMTi).
also
discuss
summarize
current
drugs
preclinical
trials,
offering
insights
their
potential
improving
outcomes
patients.
Development,
Journal Year:
2024,
Volume and Issue:
151(13)
Published: June 17, 2024
Neural
crest
cells
are
a
stem
cell
population
unique
to
vertebrate
embryos
that
retains
broad
multi-germ
layer
developmental
potential
through
neurulation.
Much
remains
be
learned
about
the
genetic
and
epigenetic
mechanisms
control
potency
of
neural
cells.
Here,
we
examine
role
readers
BET
(bromodomain
extra
terminal)
family
play
in
controlling
pluripotent
blastula
We
find
inhibiting
activity
leads
loss
pluripotency
at
stages
neurula
stages.
compare
effects
HDAC
(an
eraser
acetylation
marks)
(a
reader
acetylation)
inhibition
they
lead
similar
cellular
outcomes
distinct
on
transcriptome.
Interestingly,
undergoing
lineage
restriction
is
coupled
increased
expression
genes
linked
prolongs
competence
initially
transit
progenitor
state.
Together
these
findings
advance
our
understanding
formation
crest.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(16), P. 12669 - 12669
Published: Aug. 11, 2023
The
bromodomain
and
extra-terminal
domain
(BET)
family
inhibitors
are
small
molecules
that
target
the
dysregulated
epigenetic
readers,
BRD2,
BRD3,
BRD4
BRDT,
at
various
transcription-related
sites,
including
super-enhancers.
BET
currently
under
investigation
both
in
pre-clinical
cell
culture
tumor-bearing
animal
models,
as
well
clinical
trials.
However,
is
case
with
other
chemotherapeutic
modalities,
development
of
resistance
likely
to
constrain
therapeutic
benefits
this
strategy.
One
tumor
survival
mechanism
has
been
studied
for
decades
autophagy.
Although
four
different
functions
autophagy
have
identified
literature
(cytoprotective,
cytotoxic,
cytostatic
non-protective),
primarily
cytoprotective
cytotoxic
forms
appear
function
experimental
models
exposed
(with
some
evidence
form).
This
review
provides
an
overview
cytoprotective,
response
models.
Our
aim
determine
whether
targeting
or
modulation
could
represent
effective
strategy
enhance
these
modalities
also
potentially
overcome
inhibition.
Current Cancer Drug Targets,
Journal Year:
2024,
Volume and Issue:
24(9), P. 930 - 940
Published: Jan. 25, 2024
Small
cell
lung
cancer
(SCLC)
has
a
dismal
prognosis.
In
addition
to
the
inactivation
of
tumor
suppressors
TP53
and
RB1,
tumor-promoting
MYC
paralogs
are
frequently
overexpressed
in
this
neuroendocrine
carcinoma.
SCLC
exhibits
high
resistance
second-line
chemotherapy
all
attempts
novel
drugs
targeted
therapy
have
failed
so
far
achieve
superior
survival.
key
roles
oncogenic
process,
orchestrating
proliferation,
apoptosis,
differentiation,
metabolism.
SCLC,
MYC-L
regulate
dedifferentiation
cells
from
Type
A
(ASCL1
expression)
other
subtypes.
Targeting
suppress
growth
is
difficult
due
lack
suitable
binding
pockets
most
advanced
miniprotein
inhibitor
Omomyc
limited
efficacy.
may
be
indirectly
Cellular and Molecular Life Sciences,
Journal Year:
2024,
Volume and Issue:
81(1)
Published: July 9, 2024
Nod-like
receptor
family
pyrin-containing
protein
3
(NLRP3)
inflammasome
plays
a
pathologic
role
in
metabolic
dysfunction-associated
steatohepatitis
(MASH),
but
the
molecular
mechanism
regulating
NLRP3
activation
hepatocellular
lipotoxicity
remains
largely
unknown.
Bromodomain-containing
4
(BRD4)
has
emerged
as
key
epigenetic
reader
of
acetylated
lysine
residues
enhancer
regions
that
control
transcription
genes.
The
aim
this
study
is
to
investigate
if
and
how
BRD4
regulated
pyroptosis
MASH.
Using
AML12
primary
mouse
hepatocytes
stimulated
by
palmitic
acid
(PA)
an
vitro
model
lipotoxicity,
we
found
targeting
genetic
knockdown
or
selective
inhibitor
MS417
protected
against
hepatosteatosis;
protective
effect
was
attributed
inhibiting
reducing
expression
Caspase-1,
gasdermin
D
(GSDMD),
interleukin
(IL)-1β
IL-6.
Moreover,
inhibition
limited
voltage-dependent
anion
channel-1
(VDAC1)
oligomerization
PA-treated
hepatocytes,
thereby
suppressing
activation.
Additionally,
enhanced
MASH
livers
humans.
Mechanistically,
upregulated
during
turn
modulated
active
mark
H3K27ac
at
promoter
Vdac
Gsdmd
genes,
enhancing
VDAC
GSDMD.
Altogether,
our
data
provide
novel
insights
into
mechanisms
underlying
activating
promoting
GSDMD-mediated
lipotoxicity.
Thus,
might
serve
therapeutic
target
for
treatment
