Advanced Drug Delivery Reviews,
Год журнала:
2020,
Номер
159, С. 245 - 293
Опубликована: Янв. 1, 2020
With
the
advent
of
effective
tools
to
study
lipids,
including
mass
spectrometry-based
lipidomics,
lipids
are
emerging
as
central
players
in
cancer
biology.
Lipids
function
essential
building
blocks
for
membranes,
serve
fuel
drive
energy-demanding
processes
and
play
a
key
role
signaling
molecules
regulators
numerous
cellular
functions.
Not
unexpectedly,
cells,
well
other
cell
types
tumor
microenvironment,
exploit
various
ways
acquire
extensively
rewire
their
metabolism
part
plastic
context-dependent
metabolic
reprogramming
that
is
driven
by
both
oncogenic
environmental
cues.
The
resulting
changes
fate
composition
help
cells
thrive
changing
microenvironment
supporting
functions
hallmarks,
energetics,
promoting
feedforward
signaling,
resisting
oxidative
stresses,
regulating
intercellular
communication
immune
responses.
Supported
close
connection
between
altered
lipid
pathogenic
process,
specific
profiles
unique
disease
biomarkers,
with
diagnostic,
prognostic
predictive
potential.
Multiple
preclinical
studies
illustrate
translational
promise
exploiting
cancer,
critically,
have
shown
context
dependent
actionable
vulnerabilities
can
be
rationally
targeted,
particularly
combinatorial
approaches.
Moreover,
themselves
used
membrane
disrupting
agents
or
components
nanocarriers
therapeutics.
number
compounds
strategies
approaching
clinical
trials,
we
at
doorstep
hitherto
underappreciated
hallmark
promising
target
oncologist's
strategy
combat
cancer.
Cell Metabolism,
Год журнала:
2022,
Номер
35(1), С. 84 - 100.e8
Опубликована: Окт. 17, 2022
Treatment
of
triple-negative
breast
cancer
(TNBC)
remains
challenging.
Deciphering
the
orchestration
metabolic
pathways
in
regulating
ferroptosis
will
provide
new
insights
into
TNBC
therapeutic
strategies.
Here,
we
integrated
multiomics
data
our
large
cohort
(n
=
465)
to
develop
atlas.
We
discovered
that
TNBCs
had
heterogeneous
phenotypes
ferroptosis-related
metabolites
and
pathways.
The
luminal
androgen
receptor
(LAR)
subtype
was
characterized
by
upregulation
oxidized
phosphatidylethanolamines
glutathione
metabolism
(especially
GPX4),
which
allowed
utilization
GPX4
inhibitors
induce
ferroptosis.
Furthermore,
verified
inhibition
not
only
induced
tumor
but
also
enhanced
antitumor
immunity.
combination
anti-PD1
possessed
greater
efficacy
than
monotherapy.
Clinically,
higher
expression
correlated
with
lower
cytolytic
scores
worse
prognosis
immunotherapy
cohorts.
Collectively,
this
study
demonstrated
landscape
revealed
an
innovative
strategy
for
refractory
LAR
tumors.
Cancer Research,
Год журнала:
2021,
Номер
81(6), С. 1583 - 1594
Опубликована: Янв. 22, 2021
Abstract
Ferroptosis
is
a
type
of
programmed
cell
death
induced
by
the
accumulation
lipid
peroxidation
and
reactive
oxygen
species
in
cells.
It
has
been
recently
demonstrated
that
cancer
cells
are
vulnerable
to
ferroptosis
inducers
(FIN).
However,
therapeutic
potential
FINs
prostate
preclinical
settings
not
explored.
In
this
study,
we
demonstrate
mediators
ferroptosis,
solute
carrier
family
7
member
11,
SLC3A2,
glutathione
peroxidase,
expressed
treatment-resistant
cancer.
We
further
sensitive
two
FINs,
erastin
RSL3.
Treatment
with
RSL3
led
significant
decrease
growth
migration
vitro
significantly
delayed
tumor
vivo,
no
measurable
side
effects.
Combination
or
standard-of-care
second-generation
antiandrogens
for
advanced
halted
vivo.
These
results
independently
combination
as
novel
strategies
Significance:
findings
reveal
induction
new
strategy
monotherapy
antiandrogens.
Cancer & Metabolism,
Год журнала:
2021,
Номер
9(1)
Опубликована: Янв. 7, 2021
Tumor
cellular
metabolism
exhibits
distinguishing
features
that
collectively
enhance
biomass
synthesis
while
maintaining
redox
balance
and
homeostasis.
These
attributes
reflect
the
complex
interactions
between
cell-intrinsic
factors
such
as
genomic-transcriptomic
regulation
cell-extrinsic
influences,
including
growth
factor
nutrient
availability.
Alongside
glucose
amino
acid
metabolism,
fatty
supports
tumorigenesis
disease
progression
through
a
range
of
processes
membrane
biosynthesis,
energy
storage
production,
generation
signaling
intermediates.
Here,
we
highlight
complexity
in
cancer,
various
inputs
outputs
intracellular
free
pool,
numerous
ways
these
pathways
influence
behavior.
