Cancer Drug Resistance,
Journal Year:
2022,
Volume and Issue:
5(3), P. 577 - 94
Published: Jan. 1, 2022
Hypoxia
is
a
common
phenomenon
in
solid
tumors
as
the
poorly
organized
tumor
vasculature
cannot
fulfill
increasing
oxygen
demand
of
rapidly
expanding
tumors.
Under
hypoxia,
cells
reshape
their
microenvironment
to
sustain
survival,
promote
metastasis,
and
develop
resistance
therapy.
Exosomes
are
extracellular
vesicles
secreted
by
most
eukaryotic
cells,
including
cells.
They
enriched
with
selective
collection
nucleic
acids
proteins
from
originating
mediate
cell-to-cell
communication.
Accumulating
evidence
suggests
that
exosomes
derived
play
critical
roles
modulating
(TME).
known
stimulate
secretion
thereby
promoting
intercellular
communication
hypoxic
surrounding
stromal
tissues.
Exosome-mediated
signaling
pathways
under
conditions
have
been
reported
cause
angiogenesis,
invasion,
drug
resistance,
immune
escape.
Recently,
programmed
cell
death
ligand-1
(PD-L1)
has
reside
transmembrane
protein
exosomes.
Exosomal
PD-L1
was
shown
suppress
T
effector
function
TME
checkpoint
This
review
provides
an
update
about
pivotal
role
tumor-derived
chemotherapy
immunotherapy,
particularly
conditions.
Emerging
strategies
target
enhance
antitumor
efficacy
discussed.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2021,
Volume and Issue:
40(1)
Published: Jan. 11, 2021
Abstract
Solid
tumors
often
grow
in
a
micro-environment
characterized
by
<
2%
O
2
tension.
This
condition,
together
with
the
aberrant
activation
of
specific
oncogenic
patwhays,
increases
amount
and
activity
hypoxia-inducible
factor-1α
(HIF-1α),
transcription
factor
that
controls
up
to
200
genes
involved
neoangiogenesis,
metabolic
rewiring,
invasion
drug
resistance.
Hypoxia
also
induces
endoplasmic
reticulum
(ER)
stress,
condition
triggers
cell
death,
if
cells
are
irreversibly
damaged,
or
survival,
stress
is
mild.
chronic
ER
both
induce
chemoresistance.
In
this
review
we
discuss
multiple
interconnected
circuitries
link
hypoxic
environment,
We
suggest
hypoxia
train
select
more
adapted
survive
unfavorable
conditions,
activating
pleiotropic
mechanisms
including
apoptosis
inhibition,
anti-oxidant
defences,
drugs
efflux.
adaptative
process
unequivocally
expands
clones
acquire
resistance
chemotherapy.
believe
pharmacological
inhibitors
HIF-1α
modulators
although
low
specificty
anti-cancer
efficacy
when
used
as
single
agents,
may
be
repurposed
chemosensitizers
against
chemorefractory
next
future.
Cell Communication and Signaling,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: Feb. 12, 2024
Abstract
Cancer
treatment
faces
many
hurdles
and
resistance
is
one
among
them.
Anti-cancer
strategies
are
evolving
due
to
innate
acquired
capacity,
governed
by
genetic,
epigenetic,
proteomic,
metabolic,
or
microenvironmental
cues
that
ultimately
enable
selected
cancer
cells
survive
progress
under
unfavorable
conditions.
Although
the
mechanism
of
drug
being
widely
studied
generate
new
target-based
drugs
with
better
potency
than
existing
ones.
However,
broader
flexibility
in
resistance,
advanced
therapeutic
options
efficacy
need
be
explored.
Combination
therapy
an
alternative
a
success
rate
though
risk
amplified
side
effects
commonplace.
Moreover,
recent
groundbreaking
precision
immune
ways
overcome
has
revolutionized
anticancer
greater
extent
only
limitation
individual-specific
needs
further
attention.
This
review
will
focus
on
challenges
opted
withstand
current
therapies
at
molecular
level
also
highlights
emerging
-like
immunological,
stem
cell-based
may
prove
have
potential
challenge
problem
resistance.
Journal of Biomedical Science,
Journal Year:
2023,
Volume and Issue:
30(1)
Published: July 31, 2023
Abstract
Dysregulating
cellular
metabolism
is
one
of
the
emerging
cancer
hallmarks.
Mitochondria
are
essential
organelles
responsible
for
numerous
physiologic
processes,
such
as
energy
production,
metabolism,
apoptosis,
and
calcium
redox
homeostasis.
Although
“Warburg
effect,”
in
which
cells
prefer
aerobic
glycolysis
even
under
normal
oxygen
circumstances,
was
proposed
a
century
ago,
how
mitochondrial
dysfunction
contributes
to
progression
still
unclear.
This
review
discusses
recent
progress
alterations
DNA
(mtDNA)
dynamics
malignant
progression.
Moreover,
we
integrate
possible
regulatory
mechanism
dysfunction–mediated
retrograde
signaling
pathways,
including
mitochondrion-derived
molecules
(reactive
species,
calcium,
oncometabolites,
mtDNA)
stress
response
pathways
(mitochondrial
unfolded
protein
integrated
response)
provide
therapeutic
targets.
Furthermore,
discuss
findings
on
role
mitochondria
immune
function
reveal
impact
tumor
microenvironment
remodeling
immunity.
Targeting
might
improve
immunotherapy.
These
suggest
that
targeting
malignancy
modulating
immunity
be
promising
treatment
strategies
patients
precise
personalized
medicine
against
cancer.
Small Methods,
Journal Year:
2024,
Volume and Issue:
8(8)
Published: Jan. 9, 2024
Abstract
Oxygen
(O
2
),
nitric
oxide
(NO),
carbon
monoxide
(CO),
hydrogen
sulfide
(H
S),
and
)
with
direct
effects,
dioxide
(CO
complementary
effects
on
the
condition
of
various
diseases
are
known
as
therapeutic
gases.
The
targeted
delivery
in
situ
generation
these
gases
controllable
release
at
site
disease
has
attracted
attention
to
avoid
risk
gas
poisoning
improve
their
performance
treating
such
cancer
therapy,
cardiovascular
bone
tissue
engineering,
wound
healing.
Stimuli‐responsive
gas‐generating
sources
systems
based
biomaterials
that
enable
on‐demand
promising
approaches
for
precise
therapy.
This
work
highlights
current
advances
design
development
new
generate
deliver
behavior.
delivered
biomedical
applications
is
then
discussed.
Journal of drug targeting,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 33
Published: Jan. 15, 2025
The
lung
tumor
microenvironment
is
composed
of
various
cell
types,
including
cancer
cells,
stromal
and
immune
as
well
extracellular
matrix
(ECM).
These
cells
surrounding
ECM
create
a
stiff,
hypoxic,
acidic,
immunosuppressive
that
can
augment
the
resistance
tumors
to
different
forms
death
facilitate
invasion
metastasis.
This
environment
induce
chemo/radiotherapy
by
inducing
anti-apoptosis
mediators
such
phosphoinositide
3-kinase
(PI3K)/Akt,
signal
transducer
activator
transcription
3
(STAT3),
nuclear
factor
κB
(NF-κB),
leading
exhaustion
antitumor
immunity
further
chemo/radiotherapy.
In
addition,
resist
boosting
multidrug
mechanisms
antioxidant
defense
systems
within
other
TME
components.
this
review,
we
discuss
interactions
communications
between
these
components
also
effects
hypoxia,
evasion,
remodeling
on
resistance.
Finally,
review
current
strategies
in
preclinical
clinical
studies,
inhibition
checkpoint
molecules,
chemoattractants,
cytokines,
growth
factors,
programmed
1
(PD-1),
insulin-like
2
(IGF-2)
for
targeting
overcome
chemotherapy
radiotherapy.
Cancer
hypoxia,
recognized
as
one
of
the
most
important
hallmarks
cancer,
affects
gene
expression,
metabolism
and
ultimately
tumor
biology-related
processes.
Major
causes
cancer
hypoxia
are
deficient
or
inappropriate
vascularization
systemic
patient
(frequently
induced
by
anemia),
leading
to
a
unique
form
genetic
reprogramming
transcription
factors
(HIF).
However,
constitutive
activation
oncogene-driven
signaling
pathways
may
also
activate
independently
oxygen
supply.
The
consequences
HIF
in
tumors
angiogenic
phenotype,
novel
metabolic
profile
immunosuppressive
microenvironment.
adaptation
mechanisms
two
major
therapy
resistance.
Accordingly,
it
seems
inevitable
combine
various
therapeutic
modalities
patients
existing
anti-hypoxic
agents
such
anti-angiogenics,
anti-anemia
therapies
specific
pathway
inhibitors.
It
is
evident
that
there
an
unmet
need
develop
targeted
improve
efficacies
anti-cancer
modalities.
case
has
been
opened
recently
due
approval
first-in-class
HIF2α
inhibitor.
Biomedicine & Pharmacotherapy,
Journal Year:
2021,
Volume and Issue:
141, P. 111875 - 111875
Published: July 3, 2021
Cancer
stands
as
one
of
the
most
leading
causes
death
worldwide,
while
significant
challenges
in
treating
it
is
revealing
novel
alternatives
to
predict,
diagnose,
and
eradicate
tumor
cell
growth.
Although
various
methods,
such
surgery,
chemotherapy,
radiation
therapy,
are
used
today
treat
cancer,
its
mortality
rate
still
high
due
numerous
shortcomings
each
approach.
Regenerative
medicine
field,
including
tissue
engineering,
gene
participate
cancer
treatment
development
models
improve
understanding
biology.
The
final
intention
convey
fundamental
laboratory
research
effective
clinical
treatments,
from
bench
bedside.
Proper
interpretation
attempts
helps
lessen
burden
illness
for
patients.
purpose
this
review
investigate
role
regenerative
accelerating
improving
treatment.
This
study
examines
capabilities
providing
treatments
effectiveness
these
clarify
path
much
possible
promote
advanced
future
field.
Theranostics,
Journal Year:
2022,
Volume and Issue:
12(10), P. 4802 - 4817
Published: Jan. 1, 2022
Background:
Chemoresistance
to
5-fluorouracil
(5-FU)
is
a
major
barrier
influence
the
treatment
efficiency
of
colorectal
cancer
(CRC)
patients,
while
precise
molecular
mechanisms
underlying
5-FU
resistance
remain
be
fully
elucidated.Methods:
The
metabolic
profiles
including
ATP
generation,
glucose
consumption,
lactate
and
oxygen
consumption
rate
(OCR)
in
resistant
CRC
cells
were
compared
with
those
their
parental
cells.Subsequently,
series
vitro
vivo
experiments
carried
out
investigate
responsible
for
reprogramming
cells.Results:
We
found
that
showed
increased
levels
OCR
as
cells.Further,
mRNA
N
6
-methyladenosine
(m
A)
methyltransferase-like
3
(METTL3)
observed
cells.Inhibition
or
knockdown
METTL3
can
suppress
glycolysis
restore
chemosensitivity
cells.Mechanistically,
enhances
expression
LDHA,
which
catalyzes
conversion
pyruvate
lactate,
trigger
resistance.METTL3
increase
transcription
LDHA
via
stabilizing
hypoxia-inducible
factor
(HIF-1α),
further,
also
triggers
translation
methylation
its
CDS
region
recruitment
YTH
domain-containing
family
protein
1
(YTHDF1).Targeted
inhibition
METTL3/LDHA
axis
significantly
sensitivity
cells.
Conclusion:Our
study
indicates
axis-induced
metabolism
potential
therapy
target
overcome
