Cancers,
Journal Year:
2025,
Volume and Issue:
17(10), P. 1681 - 1681
Published: May 16, 2025
Background/Objectives:
We
aimed
to
discover
genes
with
bimodal
expression
linked
patient
outcomes,
reveal
underlying
oncogenotypes
and
identify
new
therapeutic
insights
in
lung
adenocarcinoma
(LUAD).
Methods:
performed
meta-analysis
screen
LUAD
datasets
for
prognostic
patterns.
Kynureninase
(KYNU),
a
key
enzyme
tryptophan
catabolism,
emerged
as
top
candidate.
then
examined
its
relationship
mutations,
metabolic
alterations,
immune
microenvironment
states,
patterns
human
mouse
models
using
bulk
single-cell
transcriptomics,
metabolomics,
preclinical
model
datasets.
Pan-cancer
associations
were
also
assessed.
Results:
Model-based
clustering
of
KYNU
outperformed
median-based
dichotomization
accuracy.
was
elevated
tumors
KEAP1
STK11
co-mutations
but
remained
strong
independent
marker.
Metabolomic
analysis
showed
that
KYNU-high
had
increased
anthranilic
acid,
catalytic
product,
while
maintaining
stable
kynurenine
levels,
suggesting
compensatory
mechanism
sustaining
immunosuppressive
signaling.
Single-cell
data
cancer
cell-intrinsic
immune-cold
myeloid-derived
immune-infiltrated
tumors.
In
murine
models,
Kynu
predominantly
immune-derived
uncoupled
from
Nrf2/Lkb1
signaling,
indicating
poor
fidelity.
KYNU’s
extended
across
types,
outcomes
pancreatic
kidney
cancers
favorable
melanoma,
underscoring
the
need
lineage-specific
considerations
therapy
development.
Conclusions:KYNU
is
robust
biomarker
potential
immunometabolic
target
LUAD,
especially
co-mutated
Its
phenotype
offer
translational
potential,
though
species-specific
pose
challenges
modeling.
British Journal of Cancer,
Journal Year:
2024,
Volume and Issue:
131(4), P. 627 - 640
Published: June 3, 2024
Tumour-associated
macrophages
(TAMs)
sustain
a
tumour-supporting
and
immunosuppressive
milieu
therefore
aggravate
cancer
prognosis.
To
modify
TAM
behaviour
unlock
their
anti-tumoural
potential,
novel
TAM-reprogramming
immunotherapies
are
being
developed
at
an
accelerating
rate.
At
the
same
time,
scientific
discoveries
have
highlighted
more
sophisticated
phenotypes
with
complex
biological
functions
contradictory
prognostic
associations.
understand
evolving
clinical
landscape,
we
reviewed
current
past
clinically
evaluated
therapeutics
summarised
almost
200
agents
investigated
in
than
700
trials.
Observable
overall
trends
include
high
frequency
of
overlapping
strategies
against
therapeutic
targets,
development
to
improve
previously
ineffective
approaches
reliance
on
combinatory
for
efficacy.
However,
strong
anti-tumour
efficacy
is
uncommon,
which
encourages
re-directing
efforts
identifying
biomarkers
eligible
patient
populations
comparing
similar
treatments
earlier.
Future
endeavours
will
benefit
from
considering
shortcomings
treatment
accommodating
emerging
complexity
biology.
Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(9)
Published: Feb. 24, 2025
Conventional
dendritic
cells
(cDCs)
are
potent
antigen-presenting
(APCs)
that
integrate
signals
from
their
environment
allowing
them
to
direct
situation-adapted
immunity.
Thereby
they
harbor
great
potential
for
being
targeted
in
vaccination,
autoimmunity,
and
cancer.
Here,
we
use
fate
mapping,
functional
analyses,
comparative
cross-species
transcriptomics
show
RORγt
+
DCs
a
conserved,
functionally
versatile,
transcriptionally
distinct
type
of
DCs.
entail
various
populations
described
different
contexts
including
Janus
cells/RORγt-expressing
extrathymic
Aire-expressing
(eTACs),
subtypes
Thetis
cells,
-DC
(R-DC)
like
cDC2C
ACY3
We
response
inflammatory
triggers,
can
migrate
lymph
nodes
the
spleen
activate
naïve
CD4
T
cells.
These
findings
expand
repertoire
beyond
known
role
eTACs
inducing
cell
tolerance
self-antigens
intestinal
microbes
mice.
further
with
proinflammatory
features
accumulate
autoimmune
neuroinflammation
mice
men.
Thus,
our
work
establishes
as
immune
sentinel
exhibit
broad
spectrum
ranging
peripheral
activation
depending
on
environment.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: March 28, 2024
Arginine
and
tryptophan
are
pivotal
in
orchestrating
cytokine-driven
macrophage
polarization
immune
activation.
Specifically,
interferon-gamma
(IFN-γ)
stimulates
inducible
nitric
oxide
synthase
(iNOS)
expression),
leading
to
the
conversion
of
arginine
into
citrulline
(NO),
while
Interleukin-4
(IL4)
promotes
arginase
activation,
shifting
metabolism
toward
ornithine.
Concomitantly,
IFN-γ
triggers
indoleamine
2,3-dioxygenase
1
(IDO1)
induced
(IL4i1),
resulting
kynurenine
indole-3-pyruvic
acid.
These
metabolic
pathways
tightly
regulated
by
NAD
+
-dependent
sirtuin
proteins,
with
Sirt2
Sirt5
playing
integral
roles.
In
this
review,
we
present
novel
insights
that
augment
our
understanding
following
Mycobacterium
tuberculosis
infection,
particularly
their
relevance
responses.
Additionally,
discuss
methylation
demethylation
role
regulating
metabolism,
potentially
driving
polarization.
Cellular and Molecular Immunology,
Journal Year:
2024,
Volume and Issue:
21(11), P. 1201 - 1214
Published: Oct. 14, 2024
Invasion
and
metastasis
are
hallmarks
of
cancer.
In
addition
to
the
well-recognized
hematogenous
lymphatic
pathways
metastasis,
cancer
cell
dissemination
can
occur
via
transcoelomic
perineural
routes,
which
typical
ovarian
pancreatic
cancer,
respectively.
Macrophages
a
universal
major
component
tumor
microenvironment
and,
in
established
tumors,
promote
growth
secondary
sites.
Here,
we
review
role
tumor-associated
macrophages
(TAMs)
emphasizing
diversity
myeloid
cells
different
tissue
contexts
(lungs,
liver,
brain,
bone,
peritoneal
cavity,
nerves).
The
generally
used
models
lung
fail
capture
microenvironments.
A
better
understanding
TAM
may
pave
way
for
tailored
diagnostic
therapeutic
approaches.
Metabolites,
Journal Year:
2025,
Volume and Issue:
15(3), P. 201 - 201
Published: March 13, 2025
Background:
Tumor
cells
engage
in
continuous
self-replication
by
utilizing
a
large
number
of
resources
and
capabilities,
typically
within
an
aberrant
metabolic
regulatory
network
to
meet
their
own
demands.
This
dysregulation
leads
the
formation
tumor
microenvironment
(TME)
most
solid
tumors.
Nanomedicines,
due
unique
physicochemical
properties,
can
achieve
passive
targeting
certain
tumors
through
enhanced
permeability
retention
(EPR)
effect,
or
active
deliberate
design
optimization,
resulting
accumulation
TME.
The
use
nanomedicines
target
critical
pathways
holds
significant
promise.
However,
requires
careful
selection
relevant
drugs
materials,
taking
into
account
multiple
factors.
traditional
trial-and-error
process
is
relatively
inefficient.
Artificial
intelligence
(AI)
integrate
big
data
evaluate
delivery
efficiency
nanomedicines,
thereby
assisting
nanodrugs.
Methods:
We
have
conducted
detailed
review
key
papers
from
databases,
such
as
ScienceDirect,
Scopus,
Wiley,
Web
Science,
PubMed,
focusing
on
reprogramming,
mechanisms
action
development
metabolism,
application
AI
empowering
nanomedicines.
integrated
content
present
current
status
research
metabolism
potential
future
directions
this
field.
Results:
Nanomedicines
possess
excellent
TME
which
be
utilized
disrupt
cells,
including
glycolysis,
lipid
amino
acid
nucleotide
metabolism.
disruption
selective
killing
disturbance
Extensive
has
demonstrated
that
AI-driven
methodologies
revolutionized
nanomedicine
development,
while
concurrently
enabling
precise
identification
molecular
regulators
involved
oncogenic
reprogramming
pathways,
catalyzing
transformative
innovations
targeted
cancer
therapeutics.
Conclusions:
great
Additionally,
will
accelerate
discovery
metabolism-related
targets,
empower
optimization
help
minimize
toxicity,
providing
new
paradigm
for
development.
ACS Omega,
Journal Year:
2025,
Volume and Issue:
10(3), P. 3206 - 3221
Published: Jan. 10, 2025
Tryptanthrin
(TRYP)
is
an
indole
quinazoline
alkaloid
with
a
range
of
pharmaceutical
activities,
but
the
specific
mechanism
TRYP
against
colorectal
cancer
(CRC)
remains
obscure.
The
purpose
this
study
was
to
evaluate
antitumor
effects
on
CRC
models
both
in
vitro
and
vivo
further
analyze
its
concrete
mechanisms.
results
experiment
show
that
effectively
inhibited
proliferation
migration
SW620
cells,
arrested
cell
cycle
at
S
phase,
induced
apoptosis.
Deeply,
dramatically
increased
expression
Bax
cleaved
caspase
3
while
decreasing
Bcl-2.
transcriptome
sequencing
implied
inhibitory
were
closely
related
mitogen-activated
protein
kinase
(MAPK)
signaling
pathway,
western
blotting
verified
could
decrease
p-Erk
increase
p-p38
p-Jnk.
Besides,
our
identified
topoisomerase
I
(Topo
I)
amine
2,3-dioxygenase
1
(IDO1)
targets
TRYP.
In
vivo,
showed
different
doses
significantly
tumor
growth
mice,
degrees
necrosis
tissues,
decreased
level
Ki67
protein,
apoptotic
signal
tissues.
findings
demonstrated
CRC,
mechanisms
tightly
connected
inhibiting
activity
Topo
IDO1
regulating
MAPK
pathway.
Especially,
it
first
directly
inhibit
arrest
phase.
Therefore,
work
established
scientific
basis
for
development
Cancer Cell International,
Journal Year:
2025,
Volume and Issue:
25(1)
Published: March 13, 2025
Glioblastoma
(GBM)
ranks
among
the
most
lethal
primary
tumors
of
central
nervous
system.
This
is
partly
due
to
its
complex
intracellular
metabolism
and
interactions
with
surrounding
tumor
microenvironment
(TME).
Compelling
evidence
represents
that
altered
amino
acids
(AAs)
plays
a
crucial
role
in
both
areas.
The
AAs
their
metabolites
glioma
biology
an
emerging
topic.
Therefore,
this
review
was
conducted
summarize
current
knowledge
about
molecular
mechanisms
by
which
participate
GBM
pathogenesis.
can
directly
influence
progression
affecting
cell
or
indirectly
releasing
bioactive
agents
through
particular
metabolic
pathways.
begins
examining
pathways
essential
AAs,
such
as
tryptophan,
tyrosine,
phenylalanine,
contribute
synthesizing
critical
neurotransmitters
shape
signatures.
We
explore
how
these
impact
growth
immune
modulation,
focusing
on
promote
malignant
properties
cells.
also
play
pivotal
reprogramming
TME,
contributing
evasion
resistance
therapy.
further
discusses
signatures,
influenced
AA
metabolism,
enhance
immunosuppressive
microenvironment,
providing
new
avenues
for
targeted
immunotherapies.
Finally,
we
outline
potential
therapeutic
strategies
modulate
emphasize
opportunities
future
research
improve
management.
Cell Death and Differentiation,
Journal Year:
2024,
Volume and Issue:
31(9), P. 1113 - 1126
Published: July 26, 2024
There
is
an
unmet
clinical
need
for
pharmacologic
treatment
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD).
Hepatocyte
cell
death
a
hallmark
of
this
highly
prevalent
chronic
disease,
but
the
dominant
type
remains
uncertain.
Here
we
report
that
ferroptosis,
iron-catalyzed
mode
regulated
death,
contributes
to
MASLD.
Unsupervised
clustering
in
cohort
biopsy-proven
MASLD
patients
revealed
subgroup
with
hepatic
ferroptosis
signature
and
lower
glutathione
peroxidase
4
(GPX4)
levels.
Likewise,
reduced
defenses
was
discerned
public
transcriptomics
datasets.
Four
weeks
choline-deficient
L-amino
acid-defined
high-fat
diet
(CDAHFD)
induced
mice.
Gpx4
overexpression
did
not
affect
steatohepatitis,
instead
CDAHFD
protected
from
morbidity
due
hepatocyte-specific
knockout.
The
inhibitor
UAMC-3203
attenuated
steatosis
alanine
aminotransferase
second
model,
i.e.,
high-fructose
(HFHFD).
effect
monounsaturated
saturated
fatty
acids
supplementation
on
susceptibility
assessed
human
HepG2
cells.
Fat-laden
showed
drop
defenses,
increased
phosphatidylglycerol
two
polyunsaturated
acid
(PUFA)
lipid
tails,
sustained
sensitivity.
In
conclusion,
study
identified
as
detrimental
factor
patients.
Unexpectedly,
non-PUFA
hepatocytes
altered
bilayer
composition
maintain
Based
findings
vivo
models,
inhibition
represents
promising
therapeutic
target
Cell Death and Differentiation,
Journal Year:
2024,
Volume and Issue:
31(9), P. 1104 - 1112
Published: July 27, 2024
Ferroptosis
has
attracted
attention
throughout
the
last
decade
because
of
its
tremendous
clinical
importance.
Here,
we
review
rapidly
growing
body
literature
on
how
inhibition
ferroptosis
may
be
harnessed
for
treatment
common
diseases,
and
focus
metabolic
cardiovascular
unmet
medical
needs.
We
introduce
four
classes
preclinically
established
inhibitors
(ferrostatins)
such
as
iron
chelators,
radical
trapping
agents
that
function
in
cytoplasmic
compartment,
lipophilic
antioxidants
ninjurin-1
(NINJ1)
specific
monoclonal
antibodies.
In
contrast
to
inducers
cause
serious
untoward
effects
acute
kidney
tubular
necrosis,
side
effect
profile
ferrostatins
appears
limited.
also
consider
a
potential
itself
when
several
advanced
therapies
harnessing
small-interfering
RNA
(siRNA)-based
approaches
are
tested.
Importantly,
trial
design
is
impeded
by
lack
an
appropriate
biomarker
detection
serum
samples
or
tissue
biopsies.
However,
discuss
favorable
scenarios
suited
anti-ferroptosis
trials
test
first-in-class
compounds.
conclude
targeting
exhibits
outstanding
options
but
have
only
begun
translate
this
knowledge
into
clinically
relevant
applications.