Drug Resistance Updates,
Год журнала:
2021,
Номер
58, С. 100778 - 100778
Опубликована: Авг. 6, 2021
Drug
resistance
remains
the
major
cause
of
cancer
treatment
failure
especially
at
late
stage
disease.
However,
based
on
their
versatile
chemistry,
metal
and
metalloid
compounds
offer
possibility
to
design
fine-tuned
drugs
circumvent
even
specifically
target
drug-resistant
cells.
Based
paramount
importance
platinum
in
clinics,
two
main
areas
drug
reversal
strategies
exist:
overcoming
as
well
multidrug
ABC
efflux
pumps.
The
current
review
provides
an
overview
both
aspects
discusses
open
questions
field.
covered
this
article
involve:
1)
Altered
expression
proteins
involved
uptake,
or
intracellular
distribution,
2)
Enhanced
via
transporters,
3)
metabolism
cells,
4)
thiol
redox
homeostasis,
5)
DNA
damage
recognition
enhanced
repair,
6)
Impaired
induction
apoptosis
7)
interaction
with
immune
system.
This
represents
first
collection
(including
platinum,
ruthenium,
iridium,
gold,
copper)
(e.g.
arsenic
selenium)
which
demonstrated
activity.
A
special
focus
is
characterized
by
collateral
sensitivity
transporter-overexpressing
Through
approach,
we
wish
draw
attention
research
Future
investigations
are
warranted
obtain
more
insights
into
mechanisms
action
most
potent
specific
modalities
resistance.
Cancer Discovery,
Год журнала:
2021,
Номер
11(4), С. 838 - 857
Опубликована: Апрель 1, 2021
Immune
checkpoint
therapy
(ICT)
can
provide
durable
clinical
responses
and
improve
overall
survival.
However,
only
subsets
of
patients
with
specific
tumor
types
respond
to
ICT.
Thus,
significant
challenges
remain,
including
understanding
pathways
resistance,
optimizing
patient
selection,
improving
management
immune-related
adverse
events,
identifying
rational
therapeutic
combinations.
These
will
need
a
focused
approach
encompassing
both
basic
research,
the
integration
reverse
translational
studies.
This
integrated
lead
identification
potential
targets
for
subsequent
trials,
which
guide
decisions
as
we
develop
novel
combination
strategies
maximize
efficacy
minimize
toxicities
patients.
SIGNIFICANCE:
ICTs
induce
antitumor
cancer.
Recent
evidence
suggests
that
combinatorial
response
by
overcoming
primary
adaptive
resistance
mechanisms,
although
these
may
carry
an
increased
risk
immune-mediated
toxicities.
review
surveys
current
mechanisms
active
areas
investigation,
proposes
path
forward
minimizing
through
better
selection
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Июль 29, 2022
Abstract
Radiotherapy
(RT)
is
delivered
for
purposes
of
local
control,
but
can
also
exert
systemic
effect
on
remote
and
non-irradiated
tumor
deposits,
which
called
abscopal
effect.
The
view
RT
as
a
simple
treatment
has
dramatically
changed
in
recent
years,
it
now
widely
accepted
that
provoke
immune
response
gives
strong
rationale
the
combination
immunotherapy
(iRT).
Nevertheless,
several
points
remain
to
be
addressed
such
interaction
system,
identification
best
schedules
with
(IO),
expansion
mechanism
amplify
iRT.
To
answer
these
crucial
questions,
we
roundly
summarize
underlying
showing
whole
landscape
clinical
trials
attempt
identify
In
consideration
rarity
effect,
propose
occurrence
induced
by
radiation
promoted
100%
molecular
genetic
level.
Furthermore,
“radscopal
effect”
refers
using
low-dose
reprogram
microenvironment
may
overcome
resistance
Taken
together,
could
regarded
trigger
antitumor
response,
help
IO
used
radical
added
into
current
standard
regimen
patients
metastatic
cancer.
Cell Communication and Signaling,
Год журнала:
2022,
Номер
20(1)
Опубликована: Апрель 7, 2022
Abstract
The
main
breakthrough
in
tumor
immunotherapy
was
the
discovery
of
immune
checkpoint
(IC)
proteins,
which
act
as
a
potent
suppressor
system
by
myriad
mechanisms.
After
that,
scientists
focused
on
molecules
mainly.
Thereby,
much
effort
spent
to
progress
novel
strategies
for
suppressing
these
inhibitory
axes,
resulting
evolution
inhibitors
(ICIs).
Then,
ICIs
have
become
promising
approach
and
shaped
paradigm
shift
immunotherapies.
CTLA-4
plays
an
influential
role
attenuation
induction
naïve
memory
T
cells
engagement
with
its
responding
ligands
like
B7-1
(CD80)
B7-2
(CD86).
Besides,
PD-1
is
predominantly
implicated
adjusting
cell
function
peripheral
tissues
through
interaction
programmed
death-ligand
1
(PD-L1)
PD-L2.
Given
their
suppressive
effects
anti-tumor
immunity,
it
has
firmly
been
documented
that
based
therapies
can
be
practical
rational
therapeutic
approaches
treat
cancer
patients.
Nonetheless,
inherent
or
acquired
resistance
ICI
some
treatment-related
toxicities
restrict
application
clinic.
current
review
will
deliver
comprehensive
overview
human
tumors
alone
combination
other
modalities
support
more
desired
outcomes
lower
Drug Resistance Updates,
Год журнала:
2020,
Номер
53, С. 100718 - 100718
Опубликована: Июль 15, 2020
Cancer
is
one
of
the
main
public
health
problems
in
world.
Systemic
therapies
such
as
chemotherapy
and
more
recently
target
well
immunotherapy
have
improved
prognosis
this
large
group
complex
malignant
diseases.
However,
frequent
emergence
multidrug
resistance
(MDR)
mechanisms
major
impediments
towards
curative
treatment
cancer.
While
several
drug
chemoresistance
are
defined,
to
still
insufficiently
unclear
due
complexity
immune
response
its
dependence
on
host.
Expression
regulation
checkpoint
molecules
(such
PD-1,
CD279;
PD-L1,
CD274;
CTLA-4,
CD152)
play
a
key
role
immunotherapy.
In
regard,
based
checkpoints
inhibitors
(ICIs)
common
clinical
approach
for
patients
with
poor
when
other
first-line
failed.
Unfortunately,
about
70
%
classified
non-responders,
or
they
progress
after
initial
these
ICIs.
Multiple
factors
can
be
related
resistance:
characteristics
tumor
microenvironment
(TME);
presence
infiltrating
lymphocytes
(TILs),
CD8
+
T
cells
associated
treatment-response;
macrophages
(TAMs);
activation
certain
regulators
(like
PIK3γ
PAX4)
found
present
non-responders;
low
percentage
PD-L1
expressing
cells;
mutational
burden
(TMB);
gain
loss
antigen-presenting
molecules;
genetic
epigenetic
alterations
correlated
resistance.
This
review
provides
an
update
current
state
presenting
targets,
biomarkers
remedies
overcome
Drug Resistance Updates,
Год журнала:
2023,
Номер
68, С. 100960 - 100960
Опубликована: Март 28, 2023
Pancreatic
cancer
continues
to
be
one
of
the
world's
most
lethal
cancers.
Chemotherapy
resistance
in
patients
with
advanced
pancreatic
often
accompany
dismal
prognosis,
highlighting
need
investigate
mechanisms
drug
and
develop
therapies
overcome
chemoresistance.This
research
was
filed
Chinese
Clinical
Trial
Registry
(ChiCTR2200061320).
In
order
isolate
primary
normal
fibroblasts
(NFs)
cancer-associated
(CAFs)
samples
ductal
adenocarcinoma
(PDAC)
paracancerous
tissue
from
individuals
diagnosed
PDAC
were
obtained.
The
exosomes
obtained
using
ultracentrifugation,
their
characteristics
determined
by
Western
blotting,
nanoparticle
tracking
analysis,
transmission
electron
microscopy.
CAF-derived
miRNAs
analyzed
RT-qPCR
high-throughput
sequencing.
Gemcitabine
(GEM)
employed
promote
ferroptosis,
ferroptosis
levels
monitoring
lipid
reactive
oxygen
species
(ROS),
cell
survival,
intracellular
Fe2+
concentrations.
To
assess
vivo
tumor
response
GEM
therapy,
a
xenograft
mouse
model
utilized.Exosomes
derived
CAFs
did
not
exhibit
innate
resistance.
promoted
chemoresistance
cells
following
treatment
secreting
exosomes,
maintaining
signaling
communication
cells.
Mechanistically,
miR-3173-5p
CAF
sponged
ACSL4
inhibited
after
uptake
cells.This
work
demonstrates
novel
mode
acquired
identifies
miR-3173-5p/ACSL4
pathway
as
promising
target
for
GEM-resistant
cancer.