Cancer Medicine,
Journal Year:
2025,
Volume and Issue:
14(7)
Published: March 27, 2025
ABSTRACT
Background
Within
the
tumor
microenvironment,
cells
undergo
metabolic
reprogramming
of
cholesterol
due
to
intrinsic
cellular
alterations
and
changes
in
extracellular
milieu.
Furthermore,
within
this
microenvironment
influences
immune
landscape
tumors,
facilitating
evasion
consequently
promoting
tumorigenesis.
These
biological
involve
modifications
numerous
enzymes
associated
with
uptake
synthesis,
including
NPC1L1,
SREBP,
HMGCR,
SQLE,
PCSK9.
Review
This
review
systematically
summarizes
role
metabolism
its
cancer
progression,
examines
mechanisms
through
which
dysregulation
affects
discusses
recent
advancements
therapies
that
target
metabolism.
Conclusion
Targeting
metabolism‐related
can
inhibit
growth,
reshape
landscapes,
rejuvenate
antitumor
immunity,
offering
potential
therapeutic
avenues
treatment.
Metabolites,
Journal Year:
2022,
Volume and Issue:
12(3), P. 256 - 256
Published: March 17, 2022
Proprotein
convertase
subtilisin/kexin
type
9
(PCSK9)
is
the
last
discovered
member
of
family
proprotein
convertases
(PCs),
mainly
synthetized
in
hepatic
cells.
This
serine
protease
plays
a
pivotal
role
reduction
number
low-density
lipoprotein
receptors
(LDLRs)
on
surface
hepatocytes,
which
leads
to
an
increase
level
cholesterol
blood.
mechanism
and
fact
that
gain
function
(GOF)
mutations
PCSK9
are
responsible
for
causing
familial
hypercholesterolemia
whereas
loss-of-function
(LOF)
associated
with
hypocholesterolemia,
prompted
invention
drugs
block
action.
The
high
efficiency
inhibitors
(e.g.,
alirocumab,
evolocumab)
decreasing
cardiovascular
risk,
pleiotropic
effects
other
lipid-lowering
statins)
multifunctional
character
convertases,
were
cause
proceeding
studies
functions
beyond
metabolism.
In
this
article,
we
summarize
current
knowledge
roles
different
tissues
perspectives
its
clinical
use.
Metabolites,
Journal Year:
2022,
Volume and Issue:
12(1), P. 70 - 70
Published: Jan. 12, 2022
The
last
decades
of
research
in
cardiovascular
prevention
have
been
characterized
by
successful
bench-to-bedside
developments
for
the
treatment
low-density
lipoprotein
(LDL)
hypercholesterolemia.
Recent
examples
include
inhibition
proprotein
convertase
subtilisin/kexin
type
9
(PCSK9)
with
monoclonal
antibodies,
small
interfering
RNA
and
antisense
drugs.
cumulative
effects
LDL
cholesterol
on
atherosclerosis
make
early,
potent,
long-term
reductions
desirable-ideally
without
need
regular
intake
or
application
medication
importantly,
side
effects.
Current
reports
show
durable
primates
following
one
single
PCSK9
gene
base
editors.
Use
CRISPR/Cas
system
enables
precise
genome
editing
down
to
single-nucleotide
changes.
Provided
safety
documentation
a
reduction
events,
this
novel
technique
has
potential
fundamentally
change
our
current
concepts
prevention.
In
review,
is
explained
state
vivo
approaches
presented.
Current Atherosclerosis Reports,
Journal Year:
2022,
Volume and Issue:
24(12), P. 995 - 1004
Published: Nov. 16, 2022
Since
the
clinical
benefit
of
proprotein
convertase
subtilisin/kexin
type
9
(PCSK9)
inhibitors
occurs
in
a
setting
reducing
low-density
lipoprotein-cholesterol
(LDL-C)
to
unprecedentedly
low
levels,
it
becomes
interest
investigate
possible
adverse
effects
pertaining
risk
new-onset
diabetes
(NOD).While
safety
results
reported
either
meta-analyses
or
cardiovascular
outcome
trials
FOURIER
(with
evolocumab)
and
ODYSSEY
alirocumab)
did
not
rise
incidence
NOD,
Mendelian
randomization
analyses
were
almost
concordant
showing
an
increased
NOD.
This
evidence
was
line
with
post-marketing
reports
highlighting
that
evolocumab
alirocumab
primarily
related
mild
hyperglycaemia
rather
than
diabetes,
most
hyperglycaemic
events
occurring
during
first
6
months
treatment.
Considering
different
nature
genetic
studies
randomized
controlled
trials,
careful
monitoring
patients,
particularly
earlier
phases
treatment,
identification
those
more
susceptible
develop
treatment
PCSK9
should
be
minimal
concern.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2023,
Volume and Issue:
42(1)
Published: Jan. 2, 2023
PCSK9
regulates
cholesterol
homeostasis
and
promotes
tumorigenesis.
However,
the
relevance
of
these
two
actions
mechanisms
underlying
PCSK9's
oncogenic
roles
in
melanoma
other
cancers
remain
unclear.PCSK9's
association
with
was
analysed
using
TCGA
dataset.
Empty
vector
(EV),
PCSK9,
gain-of-function
(D374Y),
loss-of-function
(Q152H)
mutant
were
stably-expressed
murine
B16
cells
studied
for
impact
on
cell-derived
oncogenesis
vitro
vivo
syngeneic
C57BL/6
Pcsk9-/-
mice.
Intratumoral
accumulation
determined.
RNA-seq
performed
individual
tumor
types.
Differentially-expressed
genes
(DEGs)
derived
from
comparisons
D374Y,
or
Q152H
tumors
to
EV
allografts
pathway
alterations.PCSK9
expression
its
network
negatively
correlated
survival
probability
patients
melanoma.
promoted
cell
proliferation,
migration,
growth
soft
agar
vitro,
formation
mice
vivo,
intratumoral
a
manner
reflecting
regulation
low-density
lipoprotein
receptor
(LDLR):
Q152H,
EV,
D374Y.
Tumor-associated
T
cells,
CD8
+
NK
significantly
increased
D374Y
along
upregulations
multiple
immune
checkpoints,
IFNγ,
143
associated
dysfunction.
Overlap
36
between
DEGs
predicted
poor
prognosis
resistance
checkpoint
blockade
(ICB)
therapy.
CYTH4,
DENND1C,
AOAH,
TBC1D10C,
EPSTI1,
GIMAP7,
FASL
(FAS
ligand)
novel
predictors
ICB
therapy
displayed
high
level
correlations
checkpoints
across
30
human
cancers.
We
observed
FAS
ligand
being
among
most
robust
biomarkers
treatment
constructed
effective
multigene
panels
predicting
response
The
profiles
produced
by
remained
comparable
mice.Tumor-derived
plays
critical
role
pathogenesis.
are
accumulation.
systemically
affects
system,
contributing
evasion.
Novel
PCSK9-network
effectively
responses.
Best Practice & Research Clinical Endocrinology & Metabolism,
Journal Year:
2023,
Volume and Issue:
37(4), P. 101751 - 101751
Published: Feb. 24, 2023
COVID-19
infections
decrease
total
cholesterol,
LDL-C,
HDL-C,
and
apolipoprotein
A-I,
A-II,
B
levels
while
triglyceride
may
be
increased
or
inappropriately
normal
for
the
poor
nutritional
status.
The
degree
of
reduction
in
A-I
are
predictive
mortality.
With
recovery
lipid/lipoprotein
return
towards
pre-infection
studies
have
even
suggested
an
risk
dyslipidemia
post-COVID-19
infection.
potential
mechanisms
these
changes
lipid
lipoprotein
discussed.
Decreased
HDL-C
measured
many
years
prior
to
associated
with
severe
B,
Lp
(a),
were
not
consistently
risk.
Finally,
data
suggest
that
omega-3-fatty
acids
PCSK9
inhibitors
reduce
severity
infections.
Thus,
alter
affect
developing
Cancers,
Journal Year:
2023,
Volume and Issue:
15(15), P. 3948 - 3948
Published: Aug. 3, 2023
Statins,
a
class
of
HMG-CoA
reductase
inhibitors
best
known
for
their
cholesterol-reducing
and
cardiovascular
protective
activity,
have
also
demonstrated
promise
in
cancer
prevention
treatment.
This
review
focuses
on
potential
applications
head
neck
(HNC),
common
malignancy
which
established
treatment
often
fails
despite
incurring
debilitating
adverse
effects.
Preclinical
clinical
studies
suggested
that
statins
may
enhance
HNC
sensitivity
to
radiation
other
conventional
therapies
while
protecting
normal
tissue,
but
the
underlying
mechanisms
remain
poorly
defined,
likely
involving
both
cholesterol-dependent
-independent
effects
diverse
cancer-related
pathways.
brings
together
recent
discoveries
concerning
anticancer
activity
relevant
HNC,
highlighting
anti-inflammatory
impacts
DNA-damage
response.
We
explore
molecular
targets
discuss
integrate
into
regimens
improve
patient
outcomes.
Pharmaceutics,
Journal Year:
2023,
Volume and Issue:
15(2), P. 323 - 323
Published: Jan. 18, 2023
Dyslipidemia
is
listed
among
important
cardiovascular
disease
risk
factors.
Treating
lipid
disorders
difficult,
and
achieving
desirable
levels
of
LDL-cholesterol
(LDL-C)
essential
in
both
the
secondary
primary
prevention
disease.
For
many
years,
statins
became
basis
lipid-lowering
therapy.
Nevertheless,
these
drugs
are
often
insufficient
due
to
their
side
effects
restrictive
criteria
for
recommended
LDL-C
values.
Even
addition
other
drugs,
i.e.,
ezetimibe,
does
not
help
one
achieve
target
LDL-C.
The
discovery
proprotein
convertase
subtilisin/kexin
type
9
(PCSK9)
has
triggered
intensive
research
on
a
new
class
protein-based
drugs.
protein
PCSK9
located
mainly
hepatocytes
involved
metabolism
In
beginning,
antibodies
against
protein,
such
as
evolocumab,
were
invented.
next
step
was
inclisiran.
Inclisiran
small
interfering
RNA
(siRNA)
that
inhibits
expression
by
binding
specifically
mRNA
precursor
causing
its
degradation.
It
been
noticed
recent
years
siRNA
powerful
tool
biomedical
drug
discovery.
purpose
this
work
summarize
molecular
mechanisms,
pharmacokinetics,
pharmacodynamics
inclisiran
review
latest
research.
