Journal of Proteome Research,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 22, 2024
Recent
advancements
in
single-cell
(sc)
resolution
analyses,
particularly
sc
transcriptomics
and
proteomics,
have
revolutionized
our
ability
to
probe
understand
cellular
heterogeneity.
The
study
of
metabolism
through
small
molecules,
metabolomics,
provides
an
additional
level
information
otherwise
unattainable
by
or
proteomics
shedding
light
on
the
metabolic
pathways
that
translate
gene
expression
into
functional
outcomes.
Metabolic
heterogeneity,
critical
health
disease,
impacts
developmental
outcomes,
disease
progression,
treatment
responses.
However,
dedicated
approaches
probing
metabolome
not
reached
maturity
other
omics
technologies.
Over
past
decade,
innovations
metabolomics
addressed
some
practical
limitations,
including
cell
isolation,
signal
sensitivity,
throughput.
To
fully
exploit
their
potential
biological
research,
however,
remaining
challenges
must
be
thoroughly
addressed.
Additionally,
integrating
with
orthogonal
techniques
will
required
validate
relevant
results
gain
systems-level
understanding.
This
perspective
offers
a
broad-stroke
overview
recent
mass
spectrometry
(MS)-based
advancements,
focusing
ongoing
from
biologist's
viewpoint,
aimed
at
addressing
pertinent
innovative
questions.
we
emphasize
use
showcase
systems
these
sophisticated
methodologies
are
apt
explore.
Cancer Discovery,
Journal Year:
2024,
Volume and Issue:
14(6), P. 934 - 952
Published: March 29, 2024
Metastases,
which
are
the
leading
cause
of
death
in
patients
with
cancer,
have
metabolic
vulnerabilities.
Alterations
metabolism
fuel
energy
and
biosynthetic
needs
metastases
but
also
needed
to
activate
cell
state
switches
cells
invasion,
migration,
colonization,
outgrowth
distant
organs.
Specifically,
metabolites
can
protein
kinases
as
well
receptors
they
crucial
substrates
for
posttranslational
modifications
on
histone
nonhistone
proteins.
Moreover,
enzymes
moonlighting
functions
by
acting
catalytically,
mainly
kinases,
or
noncatalytically
through
protein-protein
interactions.
Here,
we
summarize
current
knowledge
signaling
cancer
metastasis.
Effective
drugs
prevention
treatment
will
an
immediate
impact
patient
survival.
To
overcome
lack
such
drugs,
a
better
understanding
molecular
processes
that
Achilles
heel
metastasizing
is
needed.
One
emerging
opportunity
changes
need
undergo
successfully
metastasize
grow
Mechanistically,
these
not
only
fulfill
biomass
demands,
often
common
between
normal
fast
proliferating
cells,
enables
particularly
important
cells.
Science Advances,
Journal Year:
2025,
Volume and Issue:
11(2)
Published: Jan. 10, 2025
The
unfolded
protein
response
(UPR)
pathway
is
crucial
for
tumorigenesis,
mainly
by
regulating
cancer
cell
stress
responses
and
survival.
However,
whether
UPR
factors
facilitate
cell-cell
communication
between
cells
immune
to
drive
progression
remains
unclear.
We
found
that
adenosine
3′,5′-monophosphate
element–binding
3–like
2
(CREB3L2),
a
noncanonical
factor,
overexpressed
activated
in
triple-negative
breast
cancer,
where
its
cleavage
releases
C-terminal
fragment
activates
the
Hedgehog
neighboring
CD8+
T
cells.
enhanced
represses
activation
inhibits
cytotoxic
effects.
Consequently,
overexpression
of
CREB3L2
not
only
promotes
tumor
growth
but
also
causes
resistance
checkpoint
blockade
(ICB).
Inhibition
impedes
CREB3L2-overexpressed
tumors
sensitizes
them
ICB
therapy.
In
summary,
we
identified
previously
unidentified
mechanism
which
dictates
cross-talk
cells,
providing
important
anticancer
therapeutic
opportunities.
Cancer Drug Resistance,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 8, 2025
Metabolic
reprogramming
within
the
tumor
microenvironment
(TME)
plays
a
critical
role
in
driving
drug
resistance
gastrointestinal
cancers
(GI),
particularly
through
pathways
of
fatty
acid
oxidation
and
glycolysis.
Cancer
cells
often
rewire
their
metabolism
to
sustain
growth
reshape
TME,
creating
conditions
such
as
nutrient
depletion,
hypoxia,
acidity
that
impair
antitumor
immune
responses.
Immune
TME
also
undergo
metabolic
alterations,
frequently
adopting
immunosuppressive
phenotypes
promote
progression
reduce
efficacy
therapies.
The
competition
for
essential
nutrients,
glucose,
between
cancer
compromises
functions
effector
cells,
T
cells.
Additionally,
by-products
like
lactate
kynurenine
further
suppress
activity
populations,
including
regulatory
M2
macrophages.
Targeting
glycolysis
presents
new
opportunities
overcome
improve
therapeutic
outcomes
GI
cancers.
Modulating
these
key
has
potential
reinvigorate
exhausted
shift
toward
phenotypes,
enhance
effectiveness
immunotherapies
other
treatments.
Future
strategies
will
require
continued
research
into
metabolism,
development
novel
inhibitors,
clinical
trials
evaluating
combination
Identifying
validating
biomarkers
be
crucial
patient
stratification
treatment
monitoring.
Insights
may
have
broader
implications
across
multiple
types,
offering
avenues
improving
treatment.
Sublethal
tumor
cells
have
an
urgent
need
for
energy,
making
it
common
them
to
switch
metabolic
phenotypes
between
glycolysis
and
oxidative
phosphorylation
(OXPHOS)
compensatory
energy
supply;
thus,
the
synchronous
interference
of
dual
pathways
limiting
level
is
essential
in
inhibiting
sublethal
growth.
Herein,
a
multifunctional
nanoplatform
Co-MOF-loaded
anethole
trithione
(ADT)
myristyl
alcohol
(MA),
modified
with
GOx
hyaluronic
acid
(HA)
was
developed,
namely,
CAMGH.
It
could
synchronously
interfere
including
OXPHOS
restrict
adenosine
triphosphate
(ATP)
supply,
achieving
inhibition
tumors
after
microwave
(MW)
thermal
therapy.
Under
low-power
MW
irradiation,
CAMGH
induced
certain
damage
while
ensuring
safety
surrounding
normal
tissues.
The
loaded
consumed
glucose
tumors,
undoubtedly
blocking
main
supply
pathway,
glycolytic
pathway.
Then,
H
Cancers,
Journal Year:
2025,
Volume and Issue:
17(3), P. 394 - 394
Published: Jan. 24, 2025
Background/Objectives:
Diffuse
large
B-cell
lymphoma
(DLBCL)
is
the
most
common
type
of
non-Hodgkin
lymphoma,
characterized
by
aggressive
and
heterogeneous
tumors
originating
from
B-cells.
Especially
in
patients
with
relapsed
or
refractory
(R/R)
disease,
DLBCL
remains
a
challenging
cancer
to
treat.
Metabolic
reprogramming
hallmark
malignant
cells.
Our
research
focuses
on
developing
strategies
enhance
clinical
outcomes
for
R/R
targeting
metabolic
vulnerabilities.
Methods:
We
investigated
effects
combining
metformin
L-asparaginase,
two
FDA-approved
antimetabolic
drugs,
cell
metabolism
survival.
Nuclear
magnetic
resonance
(NMR)
spectroscopy
was
employed
assess
disturbances
induced
drug
combination.
The
impact
lipid
metabolism,
glycolysis,
glutaminolysis,
tricarboxylic
acid
(TCA)
cycle,
antioxidant
responses
examined.
Induction
apoptosis
evaluated
FACS
analysis.
Results:
combination
L-asparaginase
strongly
sensitized
cells
apoptosis,
independently
their
oxidative
phosphorylation
(OxPhos)
BCR/glycolytic
status.
NMR
revealed
that
this
induces
broader
than
either
alone.
It
disrupts
altering
levels
phospholipids,
cholesterol,
fatty
acids.
Additionally,
it
counteracts
pro-glycolytic
effect
metformin,
decreases
reduces
glutaminolysis.
also
affects
TCA
cycle
responses,
critical
cellular
energy
production
redox
balance.
Furthermore,
interferes
key
survival
pathways,
mTORC1
MAPK
signaling.
Importantly,
proof
principle
its
beneficial
demonstrated
patients.
Conclusions:
Combining
multiple
pathways
may
represent
novel
therapeutic
approach
