Redox Biology,
Journal Year:
2024,
Volume and Issue:
79, P. 103458 - 103458
Published: Dec. 11, 2024
A
significant
clinical
challenge
in
patients
with
colorectal
cancer
(CRC),
which
adversely
impacts
patient
survival,
is
the
development
of
therapy
resistance
leading
to
a
relapse.
Therapy
and
relapse
CRC
associated
formation
lipid
droplets
(LD)
by
stimulating
de
novo
lipogenesis
(DNL).
However,
molecular
mechanisms
underlying
increase
DNL
susceptibility
DNL-targeted
therapies
remain
unclear.
Our
study
demonstrates
that
drug-tolerant
persister
cells
(DTPs)
over-express
Lipin1
(LPIN1),
facilitates
sequestration
free
fatty
acids
into
LDs.
The
increased
expression
mediated
ETS1-PTPN1-c-Src-CEBPβ
pathway.
Blocking
conversion
LDs
treatment
statins
or
inhibiting
lipin1
disrupts
homeostasis,
lipotoxicity
ferroptotic
cell
death
both
DTPs
patient-derived
organoids
(PDOs)
vitro.
Ferroptosis
inhibitors
N-acetylcysteine
(NAC)
can
alleviate
ROS
resulting
from
inhibition.
This
strategy
also
significantly
reduces
tumor
growth
DTP
mouse
xenograft
(PDX)
models.
findings
highlight
new
metabolic
vulnerability
DTPs,
PDO,
PDX
models
provide
framework
for
rational
repurposing
statins.
Targeting
phosphatidic
acid
(PA)
diacylglycerol
(DAG)
prevent
droplet
could
be
an
effective
therapeutic
approach
therapy-resistant
CRC.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(4), P. 1483 - 1483
Published: Feb. 11, 2025
Epidermal
growth
factor
receptor
tyrosine
kinase
inhibitors
(EGFR-TKIs)
have
demonstrated
remarkable
efficacy
in
treating
non-small
cell
lung
cancer
(NSCLC),
but
acquired
resistance
greatly
reduces
and
poses
a
significant
challenge
to
patients.
While
numerous
studies
investigated
the
mechanisms
underlying
EGFR-TKI
resistance,
its
complexity
diversity
make
existing
understanding
still
incomplete.
Traditional
approaches
frequently
struggle
adequately
reveal
process
of
drug
development
through
mean
value
analysis
at
overall
cellular
level.
In
recent
years,
rapid
single-cell
RNA
sequencing
technology
has
introduced
transformative
method
for
analyzing
gene
expression
changes
within
tumor
cells
resolution.
It
not
only
deepens
our
microenvironment
heterogeneity
associated
with
also
identifies
potential
biomarkers
resistance.
this
review,
we
highlight
critical
role
research,
particular
focus
on
application
exploring
EGFR-TKI-acquired
NSCLC.
We
emphasize
elucidating
mechanism
promise
informing
more
precise
personalized
treatment
strategies.
Ultimately,
approach
aims
advance
NSCLC
toward
new
era
precision
medicine.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(4), P. 1766 - 1766
Published: Feb. 19, 2025
Lung
cancer
is
a
leading
cause
of
cancer-related
mortality
worldwide,
largely
due
to
its
heterogeneity
and
intrinsic
drug
resistance.
Malignant
pleural
effusions
(MPEs)
provide
diverse
tumor
cell
populations
ideal
for
studying
these
complexities.
Although
chemotherapy
targeted
therapies
can
be
initially
effective,
subpopulations
cells
with
phenotypic
plasticity
often
survive
treatment,
eventually
developing
Here,
we
integrated
single-cell
isolation
three-dimensional
(3D)
spheroid
culture
dissect
subclonal
responses,
aiming
inform
precision
medicine
approaches.
Using
A549
lung
cells,
established
cisplatin-resistant
line
isolated
three
resistant
subclones
(Holoclone,
Meroclone,
Paraclone)
via
sorting.
In
3D
spheroids,
Docetaxel
Alimta
displayed
higher
IC50
values
than
in
2D
cultures,
suggesting
that
models
better
reflect
clinical
dosing.
Additionally,
MPE-derived
Holoclone
Paraclone
exhibited
distinct
sensitivities
Giotrif
Capmatinib,
revealing
their
heterogeneous
responses.
Molecular
analyses
confirmed
elevated
ABCB1,
ABCG2,
stem
(CSC)
markers
(OCT4,
SOX2,
CD44,
CD133),
epithelial-mesenchymal
transition
(EMT)
(E-cadherin
downregulation,
increased
Vimentin,
N-cadherin,
Twist)
subclones,
correlating
enhanced
migration
invasion.
This
approach
clarifies
the
interplay
between
heterogeneity,
CSC/EMT
phenotypes,
resistance,
providing
valuable
tool
predicting
therapeutic
responses
guiding
personalized,
combination-based
treatments.
Cellular and Molecular Immunology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 28, 2025
In
the
tumor
host,
neutrophils
may
exhibit
protumor
or
antitumor
activity.
It
is
hypothesized
that
in
response
to
host-derived
therapy-induced
factors,
adopt
diverse
functional
states
ultimately
execute
these
differential
functions.
Here,
we
provide
an
alternative
scenario
which
of
individual
cell
population
determines
overall
versus
outcome
neutrophil‒tumor
interactions.
Experimentally,
show
human
neutrophils,
are
sequentially
stimulated
with
bacteria
and
secreted
factors
from
cells,
kill
a
certain
proportion
target
cells.
However,
majority
cells
remained
resistant
this
neutrophil-mediated
killing
underwent
functional,
phenotypic
transcriptomic
switch
was
reminiscent
partial
epithelial‒to-mesenchymal
transition.
This
biological
associated
physical
escape
NK-mediated
resulted
enhanced
metastasis
lymph
nodes
preclinical
orthotopic
mouse
model.
Mechanistically,
identified
antimicrobial
neutrophil
granule
proteins
elastase
(NE)
matrix
metalloprotease-9
(MMP-9)
as
molecular
mediators
switch.
We
validated
data
patients
head
neck
cancer
bacterially
colonized
intratumoral
niches
were
enriched
for
mesenchymal
expressing
NE
MMP-9.
Our
reveal
parallel
execution
cytotoxic
prometastatic
activity
by
activated
identify
MMP-9
node
metastasis.
The
mechanism
explains
dichotomy
tumor-associated
at
level
has
implications
superinfected
cancers
dysbiotic
microenvironment.
MedComm – Oncology,
Journal Year:
2025,
Volume and Issue:
4(2)
Published: April 8, 2025
ABSTRACT
Digestive
system
tumor,
including
esophageal
gastric
intestinal
liver
pancreatic
and
cholangiocarcinoma,
are
the
most
common
tumors
worldwide
serve
as
a
major
cause
of
tumor‐related
death.
Cancer
stem
cells
(CSCs)
small
group
in
that
harbor
self‐renewal,
differentiation
abilities,
playing
crucial
role
tumor
initiation,
progression,
metastasis,
supposed
to
be
fundamental
recurrence
after
conventional
treatment.
A
comprehensive
understanding
targeting
CSCs
is
key
overcoming
tumors.
In
this
review,
focusing
on
digestive
tumors,
we
summarize
characteristics
CSCs,
review
intracellular
mechanisms
regulate
self‐renewal
functional
maintenance
stemness
pathways,
transcription
epigenetic
regulation,
metabolic
noncoding
RNAs,
demonstrate
microenvironmental
regulation
systemic
at
molecular
cellular
levels.
Finally,
recent
advances
therapy
with
CSC
their
niche
remodeling.
These
research
progress
provide
insights
into
occurrence,
development,
drug
resistance,
metastasis
offers
new
targeted
treatment
strategies
for
defeating
Cell Genomics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 100851 - 100851
Published: April 1, 2025
Cancer
progression
and
therapeutic
resistance
are
closely
linked
to
a
stemness
phenotype.
Here,
we
introduce
protein-expression-based
index
(PROTsi)
evaluate
oncogenic
dedifferentiation
in
relation
histopathology,
molecular
features,
clinical
outcomes.
Utilizing
datasets
from
the
Clinical
Proteomic
Tumor
Analysis
Consortium
across
11
tumor
types,
validate
PROTsi's
effectiveness
accurately
quantifying
stem-like
features.
Through
integration
of
PROTsi
with
multi-omics,
including
protein
post-translational
modifications,
identify
features
associated
proteins
that
act
as
active
nodes
within
transcriptional
networks,
driving
aggressiveness.
Proteins
highly
correlated
were
identified
potential
drug
targets,
both
shared
specific.
These
stemness-associated
demonstrate
predictive
value
for
outcomes,
confirmed
by
immunohistochemistry
multiple
samples.
The
findings
emphasize
efficacy
valuable
tool
selecting
crucial
step
customizing
anti-cancer
therapy
advancing
development
cures
cancer
patients.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 26, 2024
Abstract
Small-cell
lung
cancer
(SCLC)
has
a
dismal
five-year
survival
rate
of
less
than
7%,
with
limited
advances
in
first
line
treatment
over
the
past
four
decades.
Tumor-initiating
cells
(TICs)
contribute
to
resistance
and
relapse,
major
impediment
SCLC
treatment.
Here,
we
identify
Kinase
Suppressor
Ras
1
(KSR1),
molecular
scaffold
for
Raf/MEK/ERK
signaling
cascade,
as
critical
regulator
TIC
formation
tumor
initiation
vivo
.
We
further
show
that
KSR1
mediates
cisplatin
SCLC.
While
50-70%
control
after
6-week
exposure
cisplatin,
CRISPR/Cas9-mediated
knockout
prevents
>90%
ASCL1,
NeuroD1,
POU2F3
subtypes.
KO
significantly
enhances
ability
decrease
TICs
via
vitro
extreme
limiting
dilution
analysis
(ELDA),
indicating
disruption
toxicity
responsible
therapeutic
initiation.
The
prevent
resistant
H82
xenograft
supports
this
conclusion.
Previous
studies
indicate
ERK
activation
inhibits
growth
development.
observe
minimal
effect
pharmacological
inhibition
on
no
impact
ELDA.
However,
mutational
DEF
domain,
which
interaction
ERK,
suggests
is
essential
KSR1-driven
resistance.
These
findings
reveal
key
regulatory
protein
biology
potential
target
across
multiple
Statement
Implication
Genetic
manipulation
small-cell
reveals
its
contribution
