Cancer Letters,
Год журнала:
2024,
Номер
597, С. 217064 - 217064
Опубликована: Июнь 14, 2024
Platinum-based
chemotherapy
causes
genetic
damage
and
induces
apoptosis
in
ovarian
cancer
cells.
Enhancing
the
ability
to
resist
platinum
drug-induced
DNA
apoptotic
stress
is
critical
for
tumor
cells
acquire
drug
resistance.
Here,
we
found
that
Y-box
binding
protein
1
(YBX1)
was
highly
expressed
cisplatin-resistant
patient-derived
organoids
(PDOs)
a
crucial
gene
alleviating
platinum-induced
maintaining
resistance
characteristics
Mechanistically,
YBX1
recognized
m5C
modifications
CHD3
mRNA
maintained
stability
by
recruiting
PABPC1
protein.
This
regulatory
process
enhanced
chromatin
accessibility
improved
efficiency
of
homologous
recombination
(HR)
repair,
facilitating
withstand
stress.
In
addition,
SU056,
an
inhibitor
YBX1,
exhibited
potential
reverse
subcutaneous
PDO
orthotopic
xenograft
models.
conclusion,
alleviate
may
be
target
reversing
drug-resistant
therapies.
Genes & Development,
Год журнала:
2022,
Номер
36(5-6), С. 278 - 293
Опубликована: Март 1, 2022
DNA
repair
and
damage
signaling
pathways
are
critical
for
the
maintenance
of
genomic
stability.
Defects
contribute
to
tumorigenesis,
but
also
render
cancer
cells
vulnerable
reliant
on
remaining
activities.
Here,
we
review
major
classes
defects
in
cancer,
instability
that
they
give
rise
to,
therapeutic
strategies
exploit
resulting
vulnerabilities.
Furthermore,
discuss
impacts
both
targeted
therapy
immunotherapy,
highlight
emerging
principles
targeting
therapy.
Molecular Cell,
Год журнала:
2022,
Номер
82(24), С. 4664 - 4680.e9
Опубликована: Ноя. 30, 2022
POLQ
is
a
key
effector
of
DSB
repair
by
microhomology-mediated
end-joining
(MMEJ)
and
overexpressed
in
many
cancers.
inhibitors
confer
synthetic
lethality
HR
Shieldin-deficient
cancer
cells,
which
has
been
proposed
to
reflect
critical
dependence
on
the
pathway
MMEJ.
Whether
also
operates
independent
MMEJ
remains
unexplored.
Here,
we
show
that
POLQ-deficient
cells
accumulate
post-replicative
ssDNA
gaps
upon
BRCA1/2
loss
or
PARP
inhibitor
treatment.
Biochemically,
cooperation
between
helicase
polymerase
activities
promotes
RPA
displacement
ssDNA-gap
fill-in,
respectively.
capable
gap
skipping
(MMGS),
generates
deletions
during
resemble
genomic
scars
prevalent
overexpressing
Our
findings
implicate
mutagenic
sealing,
could
drive
genome
evolution
whose
places
dependency
for
protection
cellular
viability.
Science,
Год журнала:
2023,
Номер
381(6658), С. 653 - 660
Опубликована: Июль 13, 2023
Nonhomologous
end-joining
(NHEJ)
and
homologous
recombination
(HR)
are
the
primary
pathways
for
repairing
DNA
double-strand
breaks
(DSBs)
during
interphase,
whereas
microhomology-mediated
(MMEJ)
has
been
regarded
as
a
backup
mechanism.
Through
CRISPR-Cas9-based
synthetic
lethal
screens
in
cancer
cells,
we
identified
subunits
of
9-1-1
complex
(RAD9A-RAD1-HUS1)
its
interacting
partner,
RHINO,
crucial
MMEJ
factors.
We
uncovered
an
unexpected
function
RHINO
restricting
to
mitosis.
accumulates
M
phase,
undergoes
Polo-like
kinase
1
(PLK1)
phosphorylation,
interacts
with
polymerase
θ
(Polθ),
enabling
recruitment
DSBs
subsequent
repair.
Additionally,
provide
evidence
that
activity
mitosis
repairs
persistent
originate
S
phase.
Our
findings
offer
insights
into
relationship
between
genes
Nature,
Год журнала:
2024,
Номер
628(8007), С. 433 - 441
Опубликована: Март 20, 2024
Abstract
An
important
advance
in
cancer
therapy
has
been
the
development
of
poly(ADP-ribose)
polymerase
(PARP)
inhibitors
for
treatment
homologous
recombination
(HR)-deficient
cancers
1–6
.
PARP
trap
PARPs
on
DNA.
The
trapped
are
thought
to
block
replisome
progression,
leading
formation
DNA
double-strand
breaks
that
require
HR
repair
7
Here
we
show
PARP1
functions
together
with
TIMELESS
and
TIPIN
protect
early
S
phase
from
transcription–replication
conflicts.
Furthermore,
synthetic
lethality
deficiency
is
due
an
inability
damage
caused
by
conflicts,
rather
than
PARPs.
Along
these
lines,
inhibiting
transcription
elongation
rendered
HR-deficient
cells
resistant
depleting
small-interfering
RNA
was
lethal
deficiency.
Thus,
enzymatic
activity
may
suffice
efficacy
settings.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Сен. 2, 2024
Abstract
The
primary
reason
for
high
mortality
rates
among
cancer
patients
is
metastasis,
where
tumor
cells
migrate
through
the
bloodstream
from
original
site
to
other
parts
of
body.
Recent
advancements
in
technology
have
significantly
enhanced
our
comprehension
mechanisms
behind
bloodborne
spread
circulating
(CTCs).
One
critical
process,
DNA
methylation,
regulates
gene
expression
and
chromosome
stability,
thus
maintaining
dynamic
equilibrium
Global
hypomethylation
locus-specific
hypermethylation
are
examples
changes
methylation
patterns
that
pivotal
carcinogenesis.
This
comprehensive
review
first
provides
an
overview
various
processes
contribute
formation
CTCs,
including
epithelial-mesenchymal
transition
(EMT),
immune
surveillance,
colonization.
We
then
conduct
in-depth
analysis
how
modifications
within
CTCs
impact
each
these
stages
during
CTC
dissemination.
Furthermore,
we
explored
potential
clinical
implications
with
cancer.
By
understanding
epigenetic
modifications,
can
gain
insights
into
metastatic
process
identify
new
biomarkers
early
detection,
prognosis,
targeted
therapies.
aims
bridge
gap
between
basic
research
application,
highlighting
significance
context
metastasis
offering
avenues
improving
patient
outcomes.
