RSC Medicinal Chemistry,
Год журнала:
2023,
Номер
15(2), С. 506 - 518
Опубликована: Дек. 7, 2023
The
emergence
of
multidrug
resistance
(MDR)
in
malignant
tumors
is
one
the
leading
threats
encountered
currently
by
many
chemotherapeutic
agents.
A
proposed
strategy
to
overcome
MDR
disable
efflux
function
P-glycoprotein
(P-gp/ABCB1),
a
critical
member
ABC
transporter
family
that
significantly
increases
various
anticancer
drugs
from
tumor
cells.
In
this
study,
structural
modification
third-generation
P-gp
inhibitor
WK-X-34
based
on
bioisosteric
and
fragment-growing
strategies
led
discovery
adamantane
derivative
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
162, С. 114643 - 114643
Опубликована: Апрель 7, 2023
Multi-drug
resistance
(MDR)
in
cancer
cells,
either
intrinsic
or
acquired
through
various
mechanisms,
significantly
hinders
the
therapeutic
efficacy
of
drugs.
Typically,
reduced
performance
drugs
is
predominantly
due
to
inherent
over
expression
ATP-binding
cassette
(ABC)
transporter
proteins
on
cell
membrane,
resulting
deprived
uptake
drugs,
augmenting
drug
detoxification,
and
DNA
repair.
In
addition
physiological
abnormalities
extensive
blood
flow,
MDR
phenotypes
exhibit
improved
apoptotic
threshold
efflux
efficiency.
These
severe
consequences
have
substantially
directed
researchers
fabrication
advanced
strategies,
such
as
co-delivery
along
with
generations
inhibitors,
augmented
dosage
regimens
frequency
administration,
well
combinatorial
treatment
options,
among
others.
this
review,
we
emphasize
different
reasons
mechanisms
responsible
for
cancer,
including
but
not
limited
known
mediated
by
permeability
glycoprotein
(P-gp)
other
pumps,
uptake,
altered
repair,
targets,
Further,
an
emphasis
specific
cancers
that
share
pathogenesis
executing
effluxed
common
provided.
Then,
aspects
related
nanomaterials-based
supramolecular
programmable
designs
(organic-
inorganic-based
materials),
physical
approaches
(light-
ultrasound-based
therapies),
are
discussed,
highlighting
unsolved
issues
future
advancements.
Finally,
summarize
review
interesting
perspectives
trends,
exploring
further
opportunities
overcome
MDR.
Abstract
The
incidence
of
nasopharyngeal
carcinoma
(NPC)
exhibits
significant
variations
across
different
ethnic
groups
and
geographical
regions,
with
Southeast
Asia
North
Africa
being
endemic
areas.
Of
note,
Epstein-Barr
virus
(EBV)
infection
is
closely
associated
almost
all
the
undifferentiated
NPC
cases.
Over
past
three
decades,
radiation
therapy
chemotherapy
have
formed
cornerstone
treatment.
However,
recent
advancements
in
immunotherapy
introduced
a
range
promising
approaches
for
managing
NPC.
In
light
these
developments,
it
has
become
evident
that
deeper
understanding
tumor
microenvironment
(TME)
crucial.
TME
serves
dual
function,
acting
as
promoter
tumorigenesis
while
also
orchestrating
immunosuppression,
thereby
facilitating
cancer
progression
enabling
immune
evasion.
Consequently,
comprehensive
comprehension
its
intricate
involvement
initiation,
progression,
metastasis
imperative
development
effective
anticancer
drugs.
Moreover,
given
complexity
inter-patient
heterogeneity,
personalized
treatment
should
be
designed
to
maximize
therapeutic
efficacy
circumvent
drug
resistance.
This
review
aims
provide
an
in-depth
exploration
within
context
EBV-induced
NPC,
particular
emphasis
on
pivotal
role
regulating
intercellular
communication
shaping
responses.
Additionally,
offers
concise
summary
resistance
mechanisms
potential
strategies
their
reversal,
specifically
relation
chemoradiation
therapy,
targeted
immunotherapy.
Furthermore,
advances
clinical
trials
pertaining
are
discussed.
Drug Resistance Updates,
Год журнала:
2023,
Номер
71, С. 101005 - 101005
Опубликована: Авг. 21, 2023
Multidrug
resistance
in
pancreatic
cancer
poses
a
significant
challenge
clinical
treatment.
Bufalin
(BA),
compound
found
secretions
from
the
glands
of
toads,
may
help
overcome
this
problem.
However,
severe
cardiotoxicity
thus
far
has
hindered
its
application.
Hence,
present
study
aimed
to
develop
cell
membrane-camouflaged
and
BA-loaded
polylactic-co-glycolic
acid
nanoparticle
(CBAP)
assess
potential
counter
chemoresistance
cancer.The
toxicity
CBAP
was
evaluated
by
electrocardiogram,
body
weight,
distress
score,
nesting
behavior
mice.
In
addition,
anticarcinoma
activity
underlying
mechanism
were
investigated
both
vitro
vivo.CBAP
significantly
mitigated
BA-mediated
acute
enhanced
sensitivity
several
drugs,
such
as
gemcitabine,
5-fluorouracil,
FOLFIRINOX.
Mechanistically,
directly
bound
nucleotide-binding
oligomerization
domain
containing
protein
2
(NOD2)
inhibited
expression
nuclear
factor
kappa-light-chain-enhancer
activated
B
cells.
This
inhibits
ATP-binding
cassette
transporters,
which
are
responsible
for
cells.Our
findings
indicate
that
NOD2.
Combining
with
standard-of-care
chemotherapeutics
represents
safe
efficient
strategy
treatment
cancer.
Drug Resistance Updates,
Год журнала:
2023,
Номер
72, С. 101016 - 101016
Опубликована: Ноя. 3, 2023
Drug
resistance
remains
a
major
challenge
in
cancer
treatment,
necessitating
the
development
of
novel
strategies
to
overcome
it.
Protein
arginine
methyltransferases
(PRMTs)
are
enzymes
responsible
for
epigenetic
methylation,
which
regulates
various
biological
and
pathological
processes,
as
result,
they
attractive
therapeutic
targets
overcoming
anti-cancer
drug
resistance.
The
ongoing
small
molecules
targeting
PRMTs
has
resulted
generation
chemical
probes
modulating
most
facilitated
clinical
treatment
advanced
oncology
targets,
including
PRMT1
PRMT5.
In
this
review,
we
summarize
mechanisms
underlying
protein
methylation
roles
specific
driving
Furthermore,
highlight
potential
implications
PRMT
inhibitors
decreasing
promote
formation
maintenance
drug-tolerant
cells
via
several
mechanisms,
altered
efflux
transporters,
autophagy,
DNA
damage
repair,
stem
cell-related
function,
epithelial-mesenchymal
transition,
disordered
tumor
microenvironment.
Multiple
preclinical
trials
have
demonstrated
that
inhibitors,
particularly
PRMT5
can
sensitize
drugs,
chemotherapeutic,
targeted
therapeutic,
immunotherapeutic
agents.
Combining
with
existing
will
be
promising
approach
enhanced
knowledge
complex
functions
guide
future
may
help
identify
new
indications.
Acta Pharmaceutica Sinica B,
Год журнала:
2024,
Номер
14(9), С. 3834 - 3854
Опубликована: Июнь 3, 2024
Immunotherapy
is
an
important
cancer
treatment
method
that
offers
hope
for
curing
patients.
While
immunotherapy
has
achieved
initial
success,
a
major
obstacle
to
its
widespread
adoption
the
inability
benefit
majority
of
The
success
or
failure
closely
linked
tumor's
immune
microenvironment.
Recently,
there
been
significant
attention
on
strategies
regulate
tumor
microenvironment
in
order
stimulate
anti-tumor
responses
immunotherapy.
distinctive
physical
properties
and
design
flexibility
nanomedicines
have
extensively
utilized
target
cells
(including
tumor-associated
macrophages
(TAMs),
T
cells,
myeloid-derived
suppressor
(MDSCs),
fibroblasts
(TAFs)),
offering
promising
advancements
In
this
article,
we
reviewed
aimed
at
targeting
various
focus
models
are
based
nanomedicines,
with
goal
inducing
enhancing
improve
It
worth
noting
combining
other
treatments,
such
as
chemotherapy,
radiotherapy,
photodynamic
therapy,
can
maximize
therapeutic
effects.
Finally,
identified
challenges
nanotechnology-mediated
needs
overcome
more
effective
nanosystems.
ACS Nano,
Год журнала:
2024,
Номер
18(26), С. 17267 - 17281
Опубликована: Июнь 13, 2024
Intrinsic
or
acquired
resistance
to
chemical
drugs
severely
limits
their
therapeutic
efficacy
in
cancer
treatment.
Various
intracellular
antioxidant
molecules,
particularly
glutathione
(GSH),
play
a
crucial
role
maintaining
redox
homeostasis
by
mitigating
the
overproduced
reactive
oxygen
species
(ROS)
due
rapid
cell
proliferation.
Notably,
these
antioxidants
also
eliminate
chemical-drug-induced
ROS,
eventually
diminishing
cytotoxicity
and
rendering
them
less
effective.
In
this
study,
we
combined
erastin,
GSH
biosynthesis
inhibitor,
with
2'-deoxy-5-fluorouridine
5'-monophosphate
sodium
salt
(FdUMP),
an
ROS-based
drug,
effectively
disrupt
reverse
chemotherapy
resistance.
Therefore,
efficient
ferroptosis
apoptosis
were
simultaneously
induced
for
enhanced
antitumor
effects.
Additionally,
employed
small
interfering
RNA
targeting
PD-L1
(siPD-L1)
as
third
agent
block
immune-checkpoint
recognition
CD8
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Фев. 14, 2024
Once
hailed
as
miraculous
solutions,
antibiotics
no
longer
hold
that
status.
The
excessive
use
of
across
human
healthcare,
agriculture,
and
animal
husbandry
has
given
rise
to
a
broad
array
multidrug-resistant
(MDR)
pathogens,
posing
formidable
treatment
challenges.
Antimicrobial
resistance
(AMR)
evolved
into
pressing
global
health
crisis,
linked
elevated
mortality
rates
in
the
modern
medical
era.
Additionally,
absence
effective
introduces
substantial
risks
surgical
procedures.
dwindling
interest
pharmaceutical
industries
developing
new
against
MDR
pathogens
aggravated
scarcity
issue,
resulting
an
exceedingly
limited
pipeline
antibiotics.
Given
these
circumstances,
imperative
devise
novel
strategies
combat
perilous
become
paramount.
Contemporary
research
unveiled
several
promising
avenues
for
addressing
this
challenge.
article
provides
comprehensive
overview
innovative
therapeutic
approaches,
highlighting
their
mechanisms
action,
benefits,
drawbacks.
