American Journal of Cancer Research,
Год журнала:
2024,
Номер
14(5), С. 2523 - 2537
Опубликована: Янв. 1, 2024
Chemotherapy
is
the
principal
treatment
for
advanced
cancer
patients.However,
chemotherapeutic
resistance,
an
important
hallmark
of
cancer,
considered
as
a
key
impediment
to
effective
therapy
in
patients.Multiple
signaling
pathways
and
factors
have
been
underscored
participate
governing
drug
resistance.Posttranslational
modifications,
including
ubiquitination,
glycosylation,
acetylation
phosphorylation,
emerged
players
modulating
resistance
gynecological
tumors,
such
ovarian
cervical
endometrial
cancer.In
this
review
article,
we
summarize
role
ubiquitination
sensitivity
cancers.Moreover,
describe
numerous
compounds
that
target
cancers
reverse
resistance.In
addition,
provide
future
perspectives
fully
elucidate
mechanisms
by
which
controls
contributing
restoring
sensitivity.This
highlights
complex
interplay
between
providing
novel
insights
into
potential
therapeutic
targets
personalized
strategies
overcome
bottleneck
resistance.
Abstract
Immune
evasion
contributes
to
cancer
growth
and
progression.
Cancer
cells
have
the
ability
activate
different
immune
checkpoint
pathways
that
harbor
immunosuppressive
functions.
The
programmed
death
protein
1
(PD-1)
cell
ligands
(PD-Ls)
are
considered
be
major
molecules.
interaction
of
PD-1
PD-L1
negatively
regulates
adaptive
response
mainly
by
inhibiting
activity
effector
T
while
enhancing
function
regulatory
(Tregs),
largely
contributing
maintenance
homeostasis
prevents
dysregulated
immunity
harmful
responses.
However,
exploit
PD-1/PD-L1
axis
cause
escape
in
development
Blockade
neutralizing
antibodies
restores
enhances
anti-tumor
immunity,
achieving
remarkable
success
therapy.
Therefore,
mechanisms
cancers
attracted
an
increasing
attention.
This
article
aims
provide
a
comprehensive
review
roles
signaling
human
autoimmune
diseases
cancers.
We
summarize
all
aspects
underlying
expression
cancers,
including
genetic,
epigenetic,
post-transcriptional
post-translational
mechanisms.
In
addition,
we
further
progress
clinical
research
on
antitumor
effects
targeting
alone
combination
with
other
therapeutic
approaches,
providing
new
strategies
for
finding
tumor
markers
developing
combined
approaches.
Abstract
Ubiquitination,
a
pivotal
posttranslational
modification
of
proteins,
plays
fundamental
role
in
regulating
protein
stability.
The
dysregulation
ubiquitinating
and
deubiquitinating
enzymes
is
common
feature
various
cancers,
underscoring
the
imperative
to
investigate
ubiquitin
ligases
deubiquitinases
(DUBs)
for
insights
into
oncogenic
processes
development
therapeutic
interventions.
In
this
review,
we
discuss
contributions
ubiquitin–proteasome
system
(UPS)
all
hallmarks
cancer
progress
drug
discovery.
We
delve
multiple
functions
UPS
oncology,
including
its
regulation
cancer-associated
pathways,
metabolic
reprogramming,
engagement
with
tumor
immune
responses,
function
phenotypic
plasticity
polymorphic
microbiomes,
other
essential
cellular
functions.
Furthermore,
provide
comprehensive
overview
novel
anticancer
strategies
that
leverage
UPS,
application
proteolysis
targeting
chimeras
(PROTACs)
molecular
glues.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Март 9, 2023
Breast
cancer
is
one
of
the
common
malignancies
with
poor
prognosis
worldwide.
The
treatment
breast
patients
includes
surgery,
radiation,
hormone
therapy,
chemotherapy,
targeted
drug
therapy
and
immunotherapy.
In
recent
years,
immunotherapy
has
potentiated
survival
certain
patients;
however,
primary
resistance
or
acquired
attenuate
therapeutic
outcomes.
Histone
acetyltransferases
induce
histone
acetylation
on
lysine
residues,
which
can
be
reversed
by
deacetylases
(HDACs).
Dysregulation
HDACs
via
mutation
abnormal
expression
contributes
to
tumorigenesis
tumor
progression.
Numerous
HDAC
inhibitors
have
been
developed
exhibited
potent
anti-tumor
activity
in
a
variety
cancers,
including
cancer.
ameliorated
immunotherapeutic
efficacy
patients.
this
review,
we
discuss
cancer,
dacinostat,
belinostat,
abexinostat,
mocetinotat,
panobinostat,
romidepsin,
entinostat,
vorinostat,
pracinostat,
tubastatin
A,
trichostatin
tucidinostat.
Moreover,
uncover
mechanisms
improving
Furthermore,
highlight
that
might
agents
potentiate
Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Март 24, 2023
Lung
cancer
is
one
of
the
common
malignant
cancers
worldwide.
Immune
checkpoint
inhibitor
(ICI)
therapy
has
improved
survival
lung
patients.
However,
ICI
leads
to
adaptive
immune
resistance
and
displays
PD-1/PD-L1
blockade
in
cancer,
leading
less
response
Tumor
microenvironment
(TME)
an
integral
tumor
microenvironment,
which
involved
immunotherapy
resistance.
Nanomedicine
been
used
enhance
cancer.
In
this
review
article,
we
described
association
between
TME
We
also
highlighted
importance
Moreover,
discussed
how
nanoparticles
are
regulation
improve
efficacy
immunotherapy,
including
SGT-53,
AZD1080,
Nanomodulator
NRF2,
Cisplatin
nanoparticles,
Au@PG,
DPAICP@ME,
SPIO
NP@M-P,
NBTXR3
ARAC
Nano-DOX,
MS
NPs,
Nab-paclitaxel,
GNPs-hPD-L1
siRNA.
Furthermore,
concluded
that
targeting
by
could
be
helpful
overcome
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 4, 2024
Immunotherapy
has
been
developed,
which
harnesses
and
enhances
the
innate
powers
of
immune
system
to
fight
disease,
particularly
cancer.
PD-1
(programmed
death-1)
PD-L1
death
ligand-1)
are
key
components
in
regulation
system,
context
cancer
immunotherapy.
regulated
by
PTMs,
including
phosphorylation,
ubiquitination,
deubiquitination,
acetylation,
palmitoylation
glycosylation.
PROTACs
(Proteolysis
Targeting
Chimeras)
a
type
new
drug
design
technology.
They
specifically
engineered
molecules
that
target
specific
proteins
within
cell
for
degradation.
have
designed
demonstrated
their
inhibitory
activity
against
PD-1/PD-L1
pathway,
showed
ability
degrade
proteins.
In
this
review,
we
describe
how
improve
efficacy
could
be
novel
strategy
combine
with
radiotherapy,
chemotherapy
immunotherapy
patients.
Acta Pharmaceutica Sinica B,
Год журнала:
2024,
Номер
14(10), С. 4312 - 4328
Опубликована: Авг. 8, 2024
Programmed
cell
death
ligand-1
(PD-L1)
is
a
T
inhibitory
immune
checkpoint
molecule
that
interacts
with
programmed
death-1
(PD-1)
to
promote
escape
of
tumor
cells.
Compared
antibody
therapies,
small
drugs
show
better
prospects
due
their
advantages
such
as
higher
bioavailability,
tissue
penetration,
and
reduced
risk
immunogenicity.
Here,
we
found
the
demethylzeylasteral
(Dem)
can
significantly
downregulate
expression
PD-L1
in
colorectal
cancer
cells
enhance
killing
effect
on
Mechanistically,
Dem
binds
deubiquitinating
enzyme
USP22
promotes
its
degradation,
resulting
increased
ubiquitination
degradation
through
proteasome
pathway.
In
addition,
activity
cytotoxic
number
myeloid-derived
suppressor
(MDSCs)
regulatory
(Tregs)
tumor-infiltrating
lymphocytes
(TILs),
thereby
activating
microenvironment
inhibiting
growth
subcutaneous
MC38
tumors
C57BL/6
mice.
Moreover,
also
combination
CTLA4
antibodies
further
improve
efficacy
antitumor
therapy.
Our
study
reveals
mechanism
by
which
suggests
may
immunotherapy.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Июль 11, 2023
With
the
rapidly
increasing
incidence
of
bladder
cancer
in
China
and
worldwide,
great
efforts
have
been
made
to
understand
detailed
mechanism
tumorigenesis.
Recently,
introduction
immune
checkpoint
inhibitor-based
immunotherapy
has
changed
treatment
strategy
for
cancer,
especially
advanced
improved
survival
patients.
The
ubiquitin–proteasome
system,
which
affects
many
biological
processes,
plays
an
important
role
cancer.
Several
E3
ubiquitin
ligases
deubiquitinases
target
checkpoints,
either
directly
or
indirectly.
In
this
review,
we
summarize
recent
progress
tumorigenesis
further
highlight
implications
immunotherapies.
