EMBO Molecular Medicine,
Год журнала:
2024,
Номер
16(5), С. 1162 - 1192
Опубликована: Апрель 24, 2024
Platinum
(PT)-resistant
Epithelial
Ovarian
Cancer
(EOC)
grows
as
a
metastatic
disease,
disseminating
in
the
abdomen
and
pelvis.
Very
few
options
are
available
for
PT-resistant
EOC
patients,
little
is
known
about
how
acquisition
of
PT-resistance
mediates
increased
spreading
capabilities
EOC.
Here,
using
isogenic
cells,
genetic
pharmacological
approaches,
patient-derived
models,
we
report
that
Integrin
α6
(ITGA6)
overexpressed
by
cells
necessary
to
sustain
ability
adhesion-dependent
PT-resistance.
Using
vitro
showed
PT
induces
positive
loop
that,
stimulating
ITGA6
transcription
secretion,
contributes
formation
pre-metastatic
niche
enabling
disseminate.
At
molecular
level,
engagement
regulates
production
availability
insulin-like
growth
factors
(IGFs),
over-stimulating
IGF1R
pathway
upregulating
Snail
expression.
In
data
were
recapitulated
vivo
models
which
targeting
prevents
dissemination
improves
PT-activity,
supporting
promising
druggable
target
patients.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Май 11, 2023
Abstract
Angiogenesis,
the
formation
of
new
blood
vessels,
is
a
complex
and
dynamic
process
regulated
by
various
pro-
anti-angiogenic
molecules,
which
plays
crucial
role
in
tumor
growth,
invasion,
metastasis.
With
advances
molecular
cellular
biology,
biomolecules
such
as
growth
factors,
chemokines,
adhesion
factors
involved
angiogenesis
has
gradually
been
elucidated.
Targeted
therapeutic
research
based
on
these
molecules
driven
treatment
to
become
promising
strategy
anti-tumor
therapy.
The
most
widely
used
agents
include
monoclonal
antibodies
tyrosine
kinase
inhibitors
(TKIs)
targeting
vascular
endothelial
factor
(VEGF)
pathway.
However,
clinical
benefit
this
modality
still
limited
due
several
defects
adverse
events,
acquired
drug
resistance,
recurrence,
lack
validated
biomarkers,
impel
further
mechanisms
angiogenesis,
development
multiple
drugs
combination
therapy
figure
out
how
improve
efficacy.
Here,
we
broadly
summarize
signaling
pathways
discuss
current
challenges
We
also
propose
approaches
efficacy
provide
perspective
for
RGD
peptide
can
be
found
in
cell
adhesion
and
signaling
proteins,
such
as
fibronectin,
vitronectin,
fibrinogen.
peptides'
principal
function
is
to
facilitate
by
interacting
with
integrin
receptors
on
the
surface.
They
have
been
intensively
researched
for
use
biotechnology
medicine,
including
incorporation
into
biomaterials,
conjugation
medicinal
molecules
or
nanoparticles,
labeling
imaging
agents.
peptides
utilized
specifically
target
cancer
cells
tumor
vasculature
engaging
these
integrins,
improving
drug
delivery
efficiency
minimizing
adverse
effects
healthy
tissues.
RGD-functionalized
carriers
are
a
viable
option
therapy
this
focused
approach
has
demonstrated
promise
future.
Writing
review
significantly
influence
how
drugs
developed
future
our
understanding
of
peptide,
finding
knowledge
gaps,
fostering
innovation,
making
design
easier.
Journal of Hematology & Oncology,
Год журнала:
2025,
Номер
18(1)
Опубликована: Янв. 13, 2025
The
tumor
microenvironment
(TME)
is
integral
to
cancer
progression,
impacting
metastasis
and
treatment
response.
It
consists
of
diverse
cell
types,
extracellular
matrix
components,
signaling
molecules
that
interact
promote
growth
therapeutic
resistance.
Elucidating
the
intricate
interactions
between
cells
TME
crucial
in
understanding
progression
challenges.
A
critical
process
induced
by
epithelial-mesenchymal
transition
(EMT),
wherein
epithelial
acquire
mesenchymal
traits,
which
enhance
their
motility
invasiveness
progression.
By
targeting
various
components
TME,
novel
investigational
strategies
aim
disrupt
TME's
contribution
EMT,
thereby
improving
efficacy,
addressing
resistance,
offering
a
nuanced
approach
therapy.
This
review
scrutinizes
key
players
emphasizing
avenues
therapeutically
components.
Moreover,
article
discusses
implications
for
resistance
mechanisms
highlights
current
toward
modulation
along
with
potential
caveats.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Авг. 17, 2023
It
has
been
known
for
decades
that
the
tumor
extracellular
matrix
(ECM)
is
dysfunctional
leading
to
loss
of
tissue
architecture
and
promotion
growth.
The
altered
ECM
fibrogenesis
leads
stiffness
act
as
a
physical
barrier
immune
cell
infiltration
into
microenvironment
(TME).
becoming
increasingly
clear
plays
important
roles
in
responses.
A
growing
body
data
now
indicates
components
also
play
more
active
role
regulation
when
dysregulated
ligands
interact
with
receptors
on
cells
inhibit
subpopulations
TME.
In
addition,
immunotherapies
such
checkpoint
inhibitors
are
approved
treat
cancer
often
hindered
by
changes.
this
review
we
highlight
ways
which
alterations
affect
regulate
immunity
cancer.
More
specifically,
how
collagens
major
components,
suppress
complex
Finally,
will
our
increased
understanding
immunotherapy
towards
novel
disruptive
strategies
overcome
suppression.
Biomedicines,
Год журнала:
2024,
Номер
12(6), С. 1163 - 1163
Опубликована: Май 24, 2024
A
relevant
challenge
for
the
treatment
of
patients
with
neoplasia
is
development
resistance
to
chemo-,
immune-,
and
radiotherapies.
Although
causes
therapy
are
poorly
understood,
evidence
suggests
it
relies
on
compensatory
mechanisms
that
cells
develop
replace
specific
intracellular
signaling
should
be
inactive
after
pharmacological
inhibition.
One
such
mechanism
involves
integrins,
membrane
receptors
connect
extracellular
matrix
have
a
crucial
role
in
cell
migration.
The
blockage
one
type
integrin
frequently
compensated
by
overexpression
another
dimer,
generally
supporting
adhesion
In
particular,
αvβ3
key
receptor
involved
tumor
treatments
tyrosine
kinase
inhibitors,
immune
checkpoint
radiotherapy;
however,
inhibition
not
enough
avoid
relapse.
Here,
we
review
been
proposed
thus
far.
Despite
our
focus
integrin,
important
note
other
integrins
also
implicated
drug
collaborative
action
between
these
neglected.
Integrins
are
transmembrane
receptors
that
play
a
crucial
role
in
cell
adhesion
and
signaling
by
connecting
the
extracellular
environment
to
intracellular
cytoskeleton.
After
binding
with
specific
ligands
matrix
(ECM),
integrins
undergo
conformational
changes
transmit
signals
across
membrane.
The
integrin-mediated
bidirectional
triggers
various
cellular
responses,
such
as
shape,
migration
proliferation.
Irregular
integrin
expression
activity
closely
linked
tumor
initiation,
angiogenesis,
motility,
invasion,
metastasis.
Thus,
understanding
intricate
regulatory
mechanism
is
essential
for
slowing
cancer
progression
preventing
carcinogenesis.
Among
four
classes
of
integrins,
arginine-glycine-aspartic
acid
(RGD)-binding
stand
out
most
receptor
subfamily
its
Dysregulation
almost
all
RGD-binding
promotes
ECM
degradation
ovarian
cancer,
resulting
carcinoma
resistance
therapy.
Preclinical
studies
have
demonstrated
targeting
these
therapeutic
antibodies
ligands,
RGD-containing
peptides
their
derivatives,
can
enhance
precision
agents
treating
cancer.
Therefore,
development
novel
This
review
mainly
discusses
genes
importance
different
subtypes,
involvement
RGD
motif-containing
proteins
carcinoma,
ongoing,
completed,
partially
unsuccessful
clinical
trials
agents,
well
existing
limitations
challenges,
advancements
made
so
far,
potential
strategies,
directions
future
research
field.
Insight
Box
Integrin-mediated
regulates
migration,
proliferation
differentiation.
Dysregulated
promote
growth
dissemination.
proper
this
complex
delay
prevent
Notably,
motifs
an
important
evolution,
small
molecules
motifs,
target
disrupt
interactions
ECM,
thereby
inhibiting
migration.
Altogether,
highlights
providing
new
insights
into
metastasis
how
been
utilized
develop
effective
treatment
plans.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 26, 2025
Abstract
Oral
submucous
fibrosis
(OSF)
is
a
chronic,
progressive,
and
fibrotic
condition
of
the
oral
mucosa
that
carries
an
elevated
risk
malignant
transformation.
We
aimed
to
identify
validate
novel
genes
associated
with
regulation
epithelial-to-mesenchymal
transition
(EMT)
in
OSF.
Genes
regulating
EMT
were
identified
through
differential
gene
expression
analysis,
using
LogFC
threshold
-1
+
1
padj
value
<
0.05,
based
on
data
from
GEO
datasets
TCGA-HNSC
datasets.
The
curated
correlated
functional
cancer
states
subjected
clustering
candidate
genes.
Integration
bioinformatics
proteomics
led
discovery
MMP9
,
SPARC
ITGA5
as
candidates.
Comprehensive
pathway
immunohistochemical
analyses
confirmed
their
roles
OSF,
squamous
cell
carcinoma
(OSCC),
OSF-associated
(OSFSCC).
significant
malignancy
suggest
mechanism
which
fibrosis-associated
type
2
undergoes
3
EMT,
driving
OSF
towards
malignancy.