Tinagl1 restores tamoxifen sensitivity and blocks fibronectin‐induced EMT by simultaneously blocking the EGFR and β1‐integrin/FAK signaling pathways in tamoxifen‐resistant breast cancer cells
IUBMB Life,
Год журнала:
2025,
Номер
77(1)
Опубликована: Янв. 1, 2025
Abstract
Tamoxifen
(TAM)
is
employed
to
treat
premenopausal
ER‐positive
breast
cancer
patients,
but
TAM
resistance
the
main
reason
affecting
its
efficacy.
Thus,
addressing
crucial
for
improving
therapeutic
outcomes.
This
study
explored
potential
role
of
Tinagl1,
a
secreted
extracellular
matrix
protein,
whose
expression
compromised
in
TAM‐resistant
MCF‐7
cells
(MCF‐7R).
We
discovered
that
Tinagl1
plays
pivotal
countering
by
inhibiting
EGFR
and
β1‐integrin/focal
adhesion
kinase
(FAK)
signaling
pathways,
both
which
are
abnormally
activated
MCF‐7R
contribute
mechanism.
Our
data
showed
level
was
lower
compared
their
wild‐type
counterparts,
could
further
reduce
cells,
consistent
with
our
microarray
results.
Moreover,
restore
sensitivity
inhibit
motility
regulating
epithelial‐mesenchymal
transition
(EMT)
vitro
vivo
experiments.
In
addition,
samples
significantly
than
matched
primary
tumors.
Analysis
an
online
database
indicated
high
correlates
better
recurrence‐free
survival
(RFS),
particularly
patients
ER‐positive,
HER2‐negative
cancer.
Overall,
this
positions
not
only
as
prognostic
marker
also
promising
target.
Язык: Английский
Understanding and Overcoming Immunotherapy Resistance in Skin Cancer: Mechanisms and Strategies
Aging and Cancer,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 14, 2025
ABSTRACT
Background
Immunotherapy
that
includes
immune
checkpoint
inhibitors
(ICI)
is
a
revolutionary
arm
of
the
treatment
skin
cancers
like
melanoma,
basal
cell
carcinoma,
and
squamous
carcinoma.
Despite
this
leap
in
clinical
advances,
critically
challenging
area
field
emerging
resistance
to
immunotherapy
limits
its
efficaciousness
profound
segment
population.
This
can
be
classified
as
primary
resistance,
which
fail
respond
initial
regimen,
or
acquired
develops
after
there
favorable
response.
A
comprehensive
understanding
basic
mechanisms
figuring
out
novel
strategies
combat
are
necessary
improve
patient
outcomes.
Methods
review
recent
studies
was
conducted
with
focus
on
preclinical
evidence
related
cancer
wide
literature
search
databases
such
PubMed,
Cochrane,
Google
Scholar
keywords,
including
“skin
cancer,”
“immunotherapy,”
“malignant
melanoma,”
“drug
resistance,”
“mechanisms,”
“strategies”
published
last
15
years.
Results
study
aims
establish
molecular
cellular
contribute
development
drug
gauge
overcome
these
barriers.
Insights
into
were
tumor‐intrinsic
factors,
genetic
epigenetic
changes,
tumor‐extrinsic
changes
tumor
microenvironment
(TME)
systemic
immunosuppression.
Therapeutic
included
combination
therapies,
newer
inhibitors,
modulation
TME
evaluated.
Key
leading
identified
include
mutations
signaling
pathways,
immunosuppressive
cells
TME,
hypoxia
contributed
resistance.
Upcoming
counteract
approaches,
adoptive
T‐cell
therapy,
immunomodulatory
agents
target
pathways.
Conclusions
There
complex
interplay
microenvironmental
leads
patients.
multi‐pronged
approach
fields
genomics
immunology
well
bioinformatics
required,
along
therapies
immunomodulators,
tackle
enhance
outcomes
for
patients
suffering
tumors.
Язык: Английский
Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword
Cancer Cell International,
Год журнала:
2025,
Номер
25(1)
Опубликована: Март 26, 2025
Abstract
Multiple
myeloma
(MM)
is
a
hematological
malignancy
defined
by
the
abnormal
proliferation
and
accumulation
of
plasma
cells
(PC)
within
bone
marrow
(BM).
While
multiple
impacts
bone,
it
not
classified
as
primary
cancer.
The
microenvironment
significantly
influences
progression
its
treatment
response.
Mesenchymal
stromal
(MSCs)
in
this
environment
engage
with
other
components
via
direct
contact
secretion
soluble
factors.
This
review
examines
established
roles
MSCs
facets
MM
pathology,
encompassing
their
pro-inflammatory
functions,
contributions
to
tumor
epigenetics,
effects
on
immune
checkpoint
inhibitors
(ICIs),
influence
reprogramming,
chemotherapy
resistance,
senescence.
investigates
role
development
MM.
Язык: Английский
Neue Ansätze in der Immuntherapie gastrointestinaler Tumoren
Deleted Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 4, 2025
Zusammenfassung
Die
Immuntherapie
ist
Teil
der
Standardtherapie
von
gastrointestinalen
(GI‑)Tumoren.
Dennoch
sind
Ansprechraten
eher
gering.
Aktuelle
Studien
untersuchen
den
optimalen
Zeitpunkt
und
die
Patientenklientel
für
eine
Immuntherapie.
Auch
Kombinationen
zugelassenen
Medikamenten
werden
getestet.
Entwicklung
neuer
Therapieansätze
ebenso
wichtig
um
z.
B.
primäre
sekundäre
Resistenzen
überwinden
zu
können.
antikörpervermittelte
Immuncheckpointinhibitor(ICI)-Therapie
wird
stetig
erweitert.
Neue
Zielmoleküle
auf
Immun-
Tumorzellen
sollen
weitere
Verbesserung
Immunantwort
durch
Aktivierung
Immunzellen
oder
Blockade
eines
hemmenden
Signalwegs
erzeugen.
Kombination
aus
Antikörper
mit
Arzneistoff
im
Sinne
Immunkonjugats
möglich.
Modifikationen
Antikörperstruktur
verbesserte
Wirksamkeit
ein
erweitertes
Einsatzspektrum
Zelluläre
Strategien,
wie
adoptive
Zelltransfer
Applikation
gentechnisch
veränderten
T‑Zellen,
aktuell
in
Einsatz
bei
GI-Tumoren
überprüft.
T‑Zellen
chimären
Antigenrezeptoren
(CAR),
bestimmte
Proteine
erkennen
angreifen,
vielversprechender
Ansatz.
Viren,
aufgrund
des
natürlichen
Reproduktionsverhaltens
genetischer
Veränderungen
zerstören
können,
als
onkolytische
Viren
GI-Onkologie
eingesetzt,
bedingen
jedoch
Herausforderungen
geringe
Immunogenität
unspezifische
Wirkung.
Eine
Schwierigkeit
sensitiver
spezifischer
Biomarker,
Ansprechen
Immuntherapien
voraussagen.
Dieser
Übersichtsartikel
soll
einen
Blick
Glaskugel
erlauben
neue
vielversprechende
immuntherapeutische
Ansätze
präsentieren
diskutieren.
Multimodal sequencing of neoadjuvant nivolumab treatment in hepatocellular carcinoma reveals cellular and molecular immune landscape for drug response
Molecular Cancer,
Год журнала:
2025,
Номер
24(1)
Опубликована: Апрель 9, 2025
A
striking
characteristic
of
liver
cancer
is
its
extensive
heterogeneity,
particularly
with
regard
to
varied
response
immunotherapy.
In
this
study,
we
employed
multimodal
sequencing
approaches
explore
the
various
aspects
neoadjuvant
nivolumab
treatment
in
patients.
We
used
spatially-resolved
transcriptomics,
single-
and
bulk-cell
TCR
clonotype
analyses
examine
spatiotemporal
dynamics
effects
nivolumab.
observed
a
significantly
higher
clonal
expansion
T
cells
tumors
patients
who
responded
treatment,
while
lipid
accumulation
was
detected
those
non-responders,
likely
due
inherent
differences
metabolic
processes.
Furthermore,
found
preferential
enrichment
cells,
which
associated
better
drug
response.
Our
results
also
indicate
functional
antagonism
between
tumor-associated
macrophages
(TAMs)
CD8
their
spatial
separation.
Notably,
identified
UBASH3B/NR1I2/CEACAM1/HAVCR2
signaling
axis,
highlighting
intense
communication
among
TAMs,
tumor
T-cells
that
leads
pro-tumorigenic
outcomes
resulting
poorer
summary,
using
integrative
investigations,
combined
multi-faceted
exploration
pre-
post-treatment
samples
nivolumab-treated
HCC
patients,
useful
mechanistic
determinants
therapeutic
reconstructed
model
recapitulates
physiological
restoration
cell
cytotoxicity
by
anti-PD1
blockade.
findings
could
provide
important
biomarkers
explain
basis
differentiating
responders
non-responders.
Язык: Английский
TRx0237 induces apoptosis and enhances anti-PD-1 immunotherapeutic efficacy in anaplastic thyroid Cancer
International Immunopharmacology,
Год журнала:
2025,
Номер
155, С. 114610 - 114610
Опубликована: Апрель 10, 2025
Язык: Английский
New Therapeutic Targets TIGIT, LAG-3 and TIM-3 in the Treatment of Advanced, Non-Small-Cell Lung Cancer
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(9), С. 4096 - 4096
Опубликована: Апрель 25, 2025
The
introduction
of
immunotherapy
and
target
therapy
into
clinical
practice
has
become
a
chance
for
many
patients
with
cancer
to
prolong
their
survival
while
maintaining
optimal
quality
life.
Treatment
lung
is
excellent
evidence
the
progress
medical
therapies.
An
understanding
mechanisms
tumor
development
led
evolution
new
methods
treatment.
Immunoreceptors
T
cells
immunoglobulin
domain
ITIM,
TIM-3
(T-cell
immunoglobulin-
mucin
domain-3-containing
molecule
3),
LAG-3
(lymphocyte
activation
gene-3)
represent
interesting
therapeutic
targets.
combination
anti-PD-1
anti-CTLA-4
blockade
proven
possibility
strengthening
anti-tumor
response
by
acting
via
two
separate
mechanisms.
Adding
additional
checkpoints
PD-1
offers
hope
further
improvements
in
effects
treatment
expanding
group
responding
immunotherapy.
This
paper
presents
promising
molecular
targets
along
studies
demonstrating
results
using
them.
Язык: Английский