Neurochemistry International,
Год журнала:
2021,
Номер
149, С. 105136 - 105136
Опубликована: Июль 16, 2021
Glioblastoma
remains
one
of
the
most
challenging
and
devastating
cancers,
with
only
a
very
small
proportion
patients
achieving
5-year
survival.
The
current
standard
care
consists
surgery,
followed
by
radiation
therapy
concurrent
maintenance
chemotherapy
alkylating
agent
temozolomide.
To
date,
this
drug
is
that
provides
significant
survival
benefit,
albeit
modest,
as
end
up
acquiring
resistance
to
drug.
As
result,
tumor
progression
recurrence
inevitably
occur,
leading
death.
Several
factors
have
been
proposed
explain
resistance,
including
an
upregulated
antioxidant
system
keep
elevated
intracellular
ROS
levels,
hallmark
cancer
cells,
under
control.
In
review,
we
discuss
mechanisms
chemoresistance
-including
important
role
glioblastoma
stem
cells-with
emphasis
on
defenses
how
agents
impair
redox
balance
(i.e.:
sulfasalazine,
erastin,
CB-839,
withaferin,
resveratrol,
curcumin,
chloroquine,
hydroxychloroquine)
might
be
advantageous
in
combined
therapies
against
type
cancer.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Янв. 1, 2021
NAD+
was
discovered
during
yeast
fermentation,
and
since
its
discovery,
important
roles
in
redox
metabolism,
aging,
longevity,
the
immune
system
DNA
repair
have
been
highlighted.
A
deregulation
of
levels
has
associated
with
metabolic
diseases
aging-related
diseases,
including
neurodegeneration,
defective
responses,
cancer.
acts
as
a
cofactor
through
interplay
NADH,
playing
an
essential
role
many
enzymatic
reactions
energy
such
glycolysis,
oxidative
phosphorylation,
fatty
acid
oxidation,
TCA
cycle.
also
plays
deacetylation
by
sirtuins
ADP
ribosylation
damage/repair
PARP
proteins.
Finally,
different
NAD
hydrolase
proteins
consume
while
converting
it
into
ADP-ribose
or
cyclic
counterpart.
Some
these
proteins,
CD38,
seem
to
be
extensively
involved
response.
Since
cannot
taken
directly
from
food,
metabolism
is
essential,
NAMPT
key
enzyme
recovering
nicotinamide
generating
most
cellular
pools.
Because
complex
network
pathways
which
enzyme,
NAMPT,
cancer
understandable.
In
present
work,
we
review
ways
that
they
may
influence
system,
stemness,
some
ongoing
research
on
therapeutic
approaches.
Journal of Clinical Investigation,
Год журнала:
2022,
Номер
132(1)
Опубликована: Янв. 3, 2022
Metabolic
inhibitors
have
been
used
in
oncology
for
decades,
dating
back
to
antimetabolites
developed
the
1940s.
In
past
25
years,
there
has
increased
recognition
of
metabolic
derangements
tumor
cells
leading
a
resurgence
interest
targeting
metabolism.
More
recently
that
drugs
metabolism
also
affect
often
acidic,
hypoxic,
immunosuppressive
microenvironment
(TME)
and
non-tumor
cell
populations
within
it,
including
immune
cells.
Here
we
review
small-molecule
currently
clinical
development
applications.
For
each
agent,
evaluate
preclinical
studies
demonstrating
antitumor
TME
effects
ongoing
trials.
The
goal
this
Review
is
provide
an
overview
landscape
oncology.
Pharmacological Reports,
Год журнала:
2023,
Номер
75(4), С. 876 - 890
Опубликована: Июнь 19, 2023
Abstract
Although
Warburg's
discovery
of
intensive
glucose
uptake
by
tumors,
followed
lactate
fermentation
in
oxygen
presence
was
made
a
century
ago,
it
is
still
an
area
intense
research
and
development
new
hypotheses
that,
layer
layer,
unravel
the
complexities
neoplastic
transformation.
This
seemingly
simple
metabolic
reprogramming
cancer
cells
reveals
intriguing,
multi-faceted
nature
that
may
link
various
phenomena
including
cell
signaling,
proliferation,
ROS
generation,
energy
supply,
macromolecules
synthesis/biosynthetic
precursor
immunosuppression,
or
cooperation
cancerous
with
cancer-associated
fibroblasts
(CAFs),
known
as
reversed
Warburg
effect.
According
to
current
perception
causes
consequences
effect,
PI3K/Akt/mTOR
are
main
signaling
pathways
concert
transcription
factors
HIF-1,
p53,
c-Myc,
modulate
activity/expression
key
regulatory
enzymes,
PKM2,
PDK1
tune
most
optimal
setting
for
cell.
turn
secures
adequate
levels
biosynthetic
precursors,
NADPH,
NAD
+
,
rapid
ATP
production
meet
increased
demands
intensively
proliferating
tumor
cells.
The
end-product
“aerobic
glycolysis”,
lactate,
oncometabolite,
provide
fuel
neighboring
cells,
facilitate
metastasis
immunosuppression
together
enabling
progression.
importance
possible
applicability
presented
issue
best
illustrated
numerous
trials
agents
targeting
constituting
promising
strategy
future
anti-cancer
regimens.
In
this
review,
we
present
aspects
multifactorial
phenomenon,
depicting
mechanisms
benefits
behind
also
pointing
selected
field
anticancer
therapy.
Molecular Oncology,
Год журнала:
2021,
Номер
15(12), С. 3242 - 3255
Опубликована: Июнь 17, 2021
Senescence
is
a
cellular
state
in
which
cells
undergo
persistent
cell
cycle
arrest
response
to
nonlethal
stress.
In
the
treatment
of
cancer,
senescence
induction
potent
method
suppressing
tumour
proliferation.
spite
this,
senescent
cancer
and
adjacent
nontransformed
microenvironment
can
remain
metabolically
active,
resulting
paradoxical
secretion
pro-inflammatory
factors,
collectively
termed
senescence-associated
secretory
phenotype
(SASP).
The
SASP
plays
critical
role
tumorigenesis,
affecting
numerous
processes
including
invasion,
metastasis,
epithelial-to-mesenchymal
transition
(EMT)
induction,
therapy
resistance
immunosuppression.
With
increasing
evidence,
it
becoming
clear
that
type,
tissue
origin
primary
stressor
are
key
determinants
how
will
influence
development
progression,
whether
be
pro-
or
antitumorigenic.
this
review,
we
focus
on
recent
evidence
regarding
therapy-induced
(TIS)
from
anticancer
agents,
chemotherapy,
radiation,
immunotherapy,
targeted
therapies,
each
trigger
SASP,
turn
influences
efficacy.
We
also
discuss
novel
pharmacological
manipulation
offers
an
exciting
contemporary
approach
therapeutics.
future
research,
these
adjuvant
options
may
help
mitigate
many
negative
side
effects
protumorigenic
roles
currently
associated
with
TIS
cancer.
Journal of Hematology & Oncology,
Год журнала:
2020,
Номер
13(1)
Опубликована: Май 19, 2020
Abstract
Gastrointestinal
cancer,
the
most
common
solid
tumor,
has
a
poor
prognosis.
With
development
of
high-throughput
sequencing
and
detection
technology,
recent
studies
have
suggested
that
many
chemical
modifications
human
RNA
are
involved
in
diseases,
including
cancer.
m
6
A,
abundant
modification,
was
revealed
to
participate
series
aspects
cancer
progression.
Recent
evidence
shown
methyltransferase-like
3
(METTL3),
first
identified
critical
methyltransferase,
catalyzes
A
methylation
on
mRNA
or
non-coding
mammals,
affecting
metabolism.
Abnormal
levels
caused
by
METTL3
been
reported
be
different
development,
proliferation,
apoptosis,
metastasis.
In
this
review,
we
will
shed
light
findings
regarding
biological
function
gastrointestinal
discuss
future
research
directions
potential
clinical
applications
for
Biomolecules,
Год журнала:
2020,
Номер
10(3), С. 358 - 358
Опубликована: Фев. 26, 2020
Actively
proliferating
cancer
cells
require
sufficient
amount
of
NADH
and
NADPH
for
biogenesis
to
protect
from
the
detrimental
effect
reactive
oxygen
species.
As
both
normal
share
same
NAD
biosynthetic
metabolic
pathways,
selectively
lowering
levels
NAD(H)
would
be
a
promising
strategy
treatment.
Targeting
nicotinamide
phosphoribosyltransferase
(NAMPT),
rate
limiting
enzyme
salvage
pathway,
affects
pool.
Similarly,
by
mutant
isocitrate
dehydrogenase
1/2
(IDH1/2)
which
produces
D-2-hydroxyglutarate
(D-2HG),
an
oncometabolite
that
downregulates
nicotinate
(NAPRT)
via
hypermethylation
on
promoter
region,
results
in
epigenetic
regulation.
is
used
generate
D-2HG,
also
needed
dihydrofolate
reductase,
target
methotrexate,
degradation.
pools
various
types
are
regulated
several
enzymes,
including
methylenetetrahydrofolate
dehydrogenase,
serine
hydroxymethyltransferase,
aldehyde
dehydrogenase.
Thus,
targeting
synthesis
under
special
circumstances
novel
approach
treat
some
cancers.
This
article
provides
rationale
key
enzymes
maintain
NAD/NADPH
pool,
reviews
preclinical
studies
these
Bioscience Reports,
Год журнала:
2022,
Номер
42(11)
Опубликована: Окт. 26, 2022
Tumours
utilise
tryptophan
(Trp)
and
its
metabolites
to
promote
their
growth
evade
host
defences.
They
recruit
Trp
through
up-regulation
of
transporters,
up-regulate
key
enzymes
degradation
down-regulate
others.
Thus,
2,3-dioxygenase
(TDO2),
indoleamine
1
(IDO1),
IDO2,
N'-formylkynurenine
formamidase
(FAMID)
Kyn
aminotransferase
(KAT1)
are
all
up-regulated
in
many
cancer
types,
whereas
monooxygenase
(KMO),
kynureninase
(KYNU),
2-amino-3-carboxymuconic
acid-6-semialdehyde
decarboxylase
(ACMSD)
quinolinate
phosphoribosyltransferase
(QPRT)
a
few,
but
down-regulated
many,
cancers.
This
results
accumulation
the
aryl
hydrocarbon
receptor
(AhR)
ligand
kynurenic
acid
depriving
NAD+
by
blocking
synthesis
from
quinolinic
acid.
The
loses
more
NAD+-consuming
poly
(ADP-ribose)
polymerases
(PARPs)
protein
acetylaters
SIRTs.
nicotinamide
arising
PARP
SIRT
activation
can
be
recycled
tumours
salvage
pathway.
Up-regulation
transporters
SLC1A5
SLC7A5
is
associated
mostly
with
that
TDO2
=
FAMID
>
KAT1
IDO2
IDO1.
serotonin
synthesis,
thereby
removing
competition
for
Strategies
combating
tumoral
immune
escape
could
involve
inhibition
transport
into
tumours,
TDO
IDOs,
FAMID,
KAT
KYNU,
NMPRT
NMNAT,
AhR,
IL-4I1,
PARPs
SIRTs,
decreasing
plasma
free
availability
albumin
infusion
or
antilipolytic
agents
glucocorticoid
induction
antagonism.
