Trends in cancer,
Год журнала:
2024,
Номер
10(9), С. 857 - 869
Опубликована: Июль 14, 2024
In
recent
years,
various
poly(ADP-ribose)
polymerase
(PARP)
inhibitors
(PARPis)
have
been
approved
for
the
treatment
of
several
cancers
to
target
vulnerability
homologous
recombination
(HR)
deficiency
(e.g.,
due
BRCA1/2
dysfunction).
this
review
we
analyze
ongoing
debates
and
breakthroughs
in
use
PARPis
BRCA1/2-deficient
cancers,
juxtaposing
'double-strand
break
(DSB)'
'single-stranded
DNA
(ssDNA)
gap'
models
synthetic
lethality
induced
by
PARPis.
We
spotlight
complexity
interaction,
highlighting
emerging
research
on
role
theta
(POLθ)
ssDNA
gaps
shaping
therapy
responses.
scrutinize
clinical
ramifications
these
findings,
especially
concerning
PARPi
efficacy
resistance
mechanisms,
underscoring
heterogeneity
BRCA-mutated
tumors
urgent
need
advanced
bridge
gap
between
laboratory
patient
outcomes.
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.
Science,
Год журнала:
2023,
Номер
380(6643), С. 382 - 387
Опубликована: Апрель 27, 2023
Replication
fork
reversal
safeguards
genome
integrity
as
a
replication
stress
response.
DNA
translocases
and
the
RAD51
recombinase
catalyze
reversal.
However,
it
remains
unknown
why
is
required
what
happens
to
machinery
during
We
find
that
uses
its
strand
exchange
activity
circumvent
replicative
helicase,
which
bound
stalled
fork.
not
for
if
helicase
unloaded.
Thus,
we
propose
creates
parental
duplex
behind
used
substrate
by
branch
migration
create
reversed
structure.
Our
data
explain
how
while
maintaining
in
position
poised
restart
synthesis
complete
duplication.
