bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 23, 2025
Abstract
Lung
cancer
is
the
leading
cause
of
cancer-related
mortality
worldwide.
Non-small
cell
lung
(NSCLC)
most
common
subtype
and
comprises
85%
cases.
Despite
treatment
advances,
local
control
after
curative-intent
chemoradiation
for
NSCLC
remains
suboptimal.
Polo-like
kinase
4
(PLK4)
a
serine-threonine
that
plays
critical
role
in
regulation
centrosome
duplication
cycle
progression
overexpressed
NSCLC,
thus,
making
it
potential
therapeutic
target.
CFI-400945
an
orally
available
PLK4
inhibitor
currently
undergoing
clinical
trial
evaluation.
As
radiation
causes
death
primarily
by
mitotic
catastrophe,
process
enhanced
alterations
amplification,
we
hypothesized
disruption
machinery
inhibition
would
enhance
effects
NSCLC.
resulted
radiosensitization
lines.
In
contrast,
had
no
effect
on
radiosensitivity
normal
fibroblasts.
did
not
affect
cell-cycle
phase
distribution
prior
to
radiation,
but
rather
combination
increased
G2/M
arrest,
concomitant
increase
through
catastrophe.
Lastly,
radiation-induced
tumor
growth
delay
xenografts.
These
data
indicate
targeting
novel
approach
sensitivity
vitro
vivo
potentiation
amplification
International Journal of Medical Sciences,
Год журнала:
2023,
Номер
20(6), С. 781 - 796
Опубликована: Янв. 1, 2023
Background:
Radiation
therapy
plays
an
important
role
in
the
treatment
of
patients
with
non-small
cell
lung
cancer
(NSCLC).
However,
radiocurability
is
greatly
limited
because
radioresistance
which
leads
to
failure,
tumor
recurrence,
and
metastasis.
Cancer
stem
(CSC)
has
been
identified
as
main
factor
that
contributes
radiation
resistance.
SOX2,
one
transcription
factors
specifically
expressed
CSC,
involved
tumorigenesis,
progression,
maintenance
stemness.
But
association
between
SOX2
NSCLC
not
clear
now.
Methods:
We
constructed
radiotherapy-resistant
line
by
multiple
radiotherapy
treatments.
Colony
formation
assay,
western
blot,
immunofluorescence
were
performed
detect
radiosensitivity
cells.
Western
qRT-PCR,
sphere
assay
used
CSC
characteristics
Wound
healing
Transwell
determine
migration
motility.
The
SOX2-upregulated
model
SOX2-downregulated
was
lentivirus
transduction.
Finally,
expression
clinical
relevance
investigated
bioinformatics
analysis
based
on
TCGA
GEO
datasets.
Results:
increased
radioresistant
cells
a
trend
dedifferentiation
observed.
results
wound
showed
overexpression
significantly
promote
invasion
Mechanistically,
enhanced
DNA
damage
repair
capability
parental
cells,
while
down-regulation
led
decreased
ability
all
related
regulated
SOX2.
In
addition,
show
high
strongly
associated
progression
poor
prognosis
NSCLC.
Conclusions:
Our
study
revealed
regulates
resistance
via
promoting
dedifferentiation.
Therefore,
may
be
promising
therapeutic
target
for
overcoming
NSCLC,
providing
new
perspective
improve
curative
effect.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 23, 2025
Abstract
Lung
cancer
is
the
leading
cause
of
cancer-related
mortality
worldwide.
Non-small
cell
lung
(NSCLC)
most
common
subtype
and
comprises
85%
cases.
Despite
treatment
advances,
local
control
after
curative-intent
chemoradiation
for
NSCLC
remains
suboptimal.
Polo-like
kinase
4
(PLK4)
a
serine-threonine
that
plays
critical
role
in
regulation
centrosome
duplication
cycle
progression
overexpressed
NSCLC,
thus,
making
it
potential
therapeutic
target.
CFI-400945
an
orally
available
PLK4
inhibitor
currently
undergoing
clinical
trial
evaluation.
As
radiation
causes
death
primarily
by
mitotic
catastrophe,
process
enhanced
alterations
amplification,
we
hypothesized
disruption
machinery
inhibition
would
enhance
effects
NSCLC.
resulted
radiosensitization
lines.
In
contrast,
had
no
effect
on
radiosensitivity
normal
fibroblasts.
did
not
affect
cell-cycle
phase
distribution
prior
to
radiation,
but
rather
combination
increased
G2/M
arrest,
concomitant
increase
through
catastrophe.
Lastly,
radiation-induced
tumor
growth
delay
xenografts.
These
data
indicate
targeting
novel
approach
sensitivity
vitro
vivo
potentiation
amplification
