British Journal of Pharmacology,
Год журнала:
2023,
Номер
180(23), С. 2937 - 2955
Опубликована: Сен. 23, 2023
Sunitinib
is
the
first-line
drug
for
renal
cell
carcinoma
(RCC)
treatment.
However,
patients
who
received
sunitinib
treatment
will
ultimately
develop
resistance
after
6-15
months,
creating
a
huge
obstacle
to
current
of
carcinoma.
Therefore,
it
urgent
clarify
mechanisms
and
new
strategies
overcome
it.
In
this
review,
in
have
been
summarized
based
on
five
topics:
activation
bypass
or
alternative
pathway,
inadequate
accumulation,
tumour
microenvironment,
metabolic
reprogramming
epigenetic
regulation.
Furthermore,
present
potential
biomarkers,
as
well
overcoming
carcinoma,
are
also
covered.
Abstract
Histones
are
DNA‐binding
basic
proteins
found
in
chromosomes.
After
the
histone
translation,
its
amino
tail
undergoes
various
modifications,
such
as
methylation,
acetylation,
phosphorylation,
ubiquitination,
malonylation,
propionylation,
butyrylation,
crotonylation,
and
lactylation,
which
together
constitute
“histone
code.”
The
relationship
between
their
combination
biological
function
can
be
used
an
important
epigenetic
marker.
Methylation
demethylation
of
same
residue,
acetylation
deacetylation,
phosphorylation
dephosphorylation,
even
methylation
different
residues
cooperate
or
antagonize
with
each
other,
forming
a
complex
network.
Histone‐modifying
enzymes,
cause
numerous
codes,
have
become
hot
topic
research
on
cancer
therapeutic
targets.
Therefore,
thorough
understanding
role
post‐translational
modifications
(PTMs)
cell
life
activities
is
very
for
preventing
treating
human
diseases.
In
this
review,
several
most
thoroughly
studied
newly
discovered
PTMs
introduced.
Furthermore,
we
focus
histone‐modifying
enzymes
carcinogenic
potential,
abnormal
modification
sites
tumors,
multiple
essential
molecular
regulation
mechanism.
Finally,
summarize
missing
areas
current
point
out
direction
future
research.
We
hope
to
provide
comprehensive
promote
further
field.
Acta Pharmaceutica Sinica B,
Год журнала:
2023,
Номер
13(6), С. 2425 - 2463
Опубликована: Фев. 18, 2023
Dysregulation
of
histone
deacetylases
(HDACs)
is
closely
related
to
tumor
development
and
progression.
As
promising
anticancer
targets,
HDACs
have
gained
a
great
deal
research
interests
two
decades
effort
has
led
the
approval
five
HDAC
inhibitors
(HDACis).
However,
currently
traditional
HDACis,
although
effective
in
approved
indications,
exhibit
severe
off-target
toxicities
low
sensitivities
against
solid
tumors,
which
urged
next-generation
HDACi.
This
review
investigates
biological
functions
HDACs,
roles
oncogenesis,
structural
features
different
isoforms,
isoform-selective
inhibitors,
combination
therapies,
multitarget
agents
PROTACs.
We
hope
these
data
could
inspire
readers
with
new
ideas
develop
novel
HDACi
good
isoform
selectivity,
efficient
effect,
attenuated
adverse
effect
reduced
drug
resistance.
Abstract
Breast
cancer
(BC)
is
the
most
frequent
malignant
diagnosis
and
a
primary
factor
for
deaths
in
women.
The
clinical
subtypes
of
BC
include
estrogen
receptor
(ER)
positive,
progesterone
(PR)
human
epidermal
growth
2
(HER2)
triple-negative
(TNBC).
Based
on
stages
BC,
various
treatment
methods
are
available
with
variations
rates
progression-free
disease
overall
survival
patients.
However,
still
faces
challenges,
particularly
terms
drug
resistance
recurrence.
study
epigenetics
has
provided
new
ideas
treating
BC.
Targeting
aberrant
epigenetic
factors
inhibitors
represents
promising
anticancer
strategy.
KDM5
family
includes
four
members,
KDM5A,
KDM5B,
KDM5C,
KDMD,
all
which
Jumonji
C
domain-containing
histone
H3K4me2/3
demethylases.
proteins
have
been
extensively
studied
where
they
involved
suppressing
or
promoting
depending
their
specific
upstream
downstream
pathways.
Several
shown
potent
inhibitory
activity
vitro
vivo,
but
challenges
exist
developing
inhibitors.
In
this
review,
we
introduce
current
therapeutic
options,
summarize
context-specific
functions
pathobiology
discuss
outlook
pitfalls
disease.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115741 - 115741
Опубликована: Окт. 19, 2023
Acetyl-coenzyme
A
(acetyl-CoA),
an
essential
metabolite,
not
only
takes
part
in
numerous
intracellular
metabolic
processes,
powers
the
tricarboxylic
acid
cycle,
serves
as
a
key
hub
for
biosynthesis
of
fatty
acids
and
isoprenoids,
but
also
signaling
substrate
acetylation
reactions
post-translational
modification
proteins,
which
is
crucial
epigenetic
inheritance
cells.
Acetyl-CoA
links
lipid
metabolism
with
histone
to
create
more
intricate
regulatory
system
that
affects
growth,
aggressiveness,
drug
resistance
malignancies
such
glioblastoma,
breast
cancer,
hepatocellular
carcinoma.
These
fascinating
advances
knowledge
acetyl-CoA
during
carcinogenesis
normal
physiology
have
raised
interest
regarding
its
modulation
malignancies.
In
this
review,
we
provide
overview
regulation
cancer
relevance
main
pathways
participates.
We
summarize
role
reprogramming
stress
cells,
well
medical
application
inhibitors
targeting
dysregulation
therapeutic
intervention
cancers.
Expert Opinion on Therapeutic Patents,
Год журнала:
2023,
Номер
33(5), С. 349 - 369
Опубликована: Май 4, 2023
Histone
deacetylase
(HDAC)
inhibitors
have
been
considered
as
an
attractive
strategy
to
reverse
aberrant
epigenetic
changes
associated
with
cancer
treatments.
The
use
of
HDAC
in
various
types
has
continued
develop
for
decades,
bringing
several
novel
successfully
into
clinical
trials.
combination
other
agents
also
developed
and
demonstrated
superior
efficacy
compared
that
monotherapy
recent
studies.
Hence,
development
new
anticancer
treatment
therapeutic
regimen
is
necessary.This
review
summarizes
a
comprehensive
the
patent
literature
from
2020
2022
including
their
(searched
European
Patent
Office,
2020-2022).
approved
developing
are
described.
It
provides
perspectives
on
challenges
future
opportunities.Although
hundreds
trials
still
going
on,
application
limited
at
present
.
Not
only
treatment,
but
non-oncology
disease
therapies
being
investigated
eagerly.
Recently,
applications
diseases
revealed
proceeded
New
indications
needed
urgently
future.
Analytical Chemistry,
Год журнала:
2024,
Номер
96(12), С. 4817 - 4824
Опубликована: Март 14, 2024
Protein
acetylation,
a
fundamental
post-translational
modification,
plays
critical
role
in
the
regulation
of
gene
expression
and
cellular
processes.
Monitoring
histone
deacetylases
(HDACs)
is
important
for
understanding
epigenetic
dynamics
advancing
early
diagnosis
malignancies.
Here,
we
leverage
dynamic
characteristics
DNA–peptide
interactions
biomimetic
nanochannels
to
develop
HDAC
detection
method.
In
specific,
catalysis
peptide
deacetylation
by
HDACs
triggers
alterations
charge
states
nanochannel
surface
accommodate
DNA
molecules.
Then,
interaction
between
peptides
shifts
from
positive
negative,
leading
reversal
ion
current
rectification
(ICR).
By
calculation
ICR
ratio,
quantitative
can
be
efficiently
achieved
using
nanochannel-based
method
an
enzyme-free
label-free
manner.
Our
experimental
results
demonstrate
that
detected
this
within
concentration
range
0.5–500
nM.
The
innate
simplicity
efficiency
strategy
may
render
it
valuable
tool
both
research
clinical
applications
realm
epigenetics
personalized
medicine.
