Poly
ADP
ribose
polymerase-1
(PARP-1)
plays
a
crucial
role
in
processes
such
as
DNA
damage
repair,
gene
transcription,
and
cell
apoptosis
cancer
cells.
Therefore,
PARP-1
represents
promising
target
to
develop
anticancer
drugs.
By
summarizing
the
structure-activity
relationship
of
inhibitors,
series
benzofuran
[3,2-D]pyrimidine-4(1H)-ketone
derivatives
containing
thiosemicarbazide
or
its
analogs
were
designed,
synthesized
biologically
evaluated
on
their
inhibition
PARP
enzyme
activity.
Among
all
compounds,
19c
exhibited
superior
biological
activity
with
IC50
values
22
nM
4.98
μM
for
exogenous
SK-OV-3
cells,
respectively,
better
than
Olaparib.
In
addition,
showed
low
toxicity
normal
liver
Anti-cancer
mechanism
studies
revealed
that
could
inhibit
repair
single-strand
breakage
aggravate
double-strand
by
inhibiting
activity,
promote
cells
through
mitochondrial
pathway.
all,
these
complexes
may
have
potential
novel
inhibitors.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(14), P. 11488 - 11521
Published: July 2, 2024
In
recent
years,
synthetic
lethality
has
been
recognized
as
a
solid
paradigm
for
anticancer
therapies.
The
discovery
of
growing
number
lethal
targets
led
to
significant
expansion
in
the
use
lethality,
far
beyond
poly(ADP-ribose)
polymerase
inhibitors
used
treat
BRCA1/2-defective
tumors.
particular,
molecular
within
DNA
damage
response
have
provided
source
that
rapidly
reached
clinical
trials.
This
Perspective
focuses
on
most
progress
and
their
inhibitors,
response,
describing
design
associated
therapeutic
strategies.
We
will
conclude
by
discussing
current
challenges
new
opportunities
this
promising
field
research,
stimulate
discussion
medicinal
chemistry
community,
allowing
investigation
reach
its
full
potential.
Life,
Journal Year:
2024,
Volume and Issue:
14(2), P. 198 - 198
Published: Jan. 30, 2024
The
treatment
landscape
of
metastatic
prostate
cancer
(mPCa)
is
rapidly
evolving
with
the
recent
approvals
poly-ADP
ribose
polymerase
inhibitors
(PARPis)
as
monotherapy
or
part
combination
therapy
androgen
receptor
pathway
in
patients
castration-resistant
(mCRPC).
Already
therapeutic
armamentarium
different
types
advanced
cancers,
these
molecules
have
shaped
a
new
era
mPCa
by
targeting
genomic
pathways
altered
patients,
leading
to
promising
responses.
These
agents
act
inhibiting
(PARP)
enzymes
involved
repairing
single-strand
breaks
DNA.
Based
on
PROfound
and
TRITON3
trials,
olaparib
rucaparib
were
respectively
approved
pretreated
mCRPC
alterations
prespecified
genes.
combinations
abiraterone
(PROpel)
niraparib
(MAGNITUDE)
first-line
options
BRCA1/2,
whereas
talazoparib
enzalutamide
(TALAPRO-2)
was
same
setting
any
HRR
genes,
which
are
found
around
quarter
cancer.
Additional
trials
already
underway
assess
an
earlier
hormone-sensitive
setting.
Future
directions
will
include
refining
sequencing
clinic
while
taking
into
account
financial
toxicity
well
potential
side
effects
encountered
therapies
elucidating
their
mechanism
action
non-altered
Herein,
we
review
biological
rationale
behind
using
PARPis
key
aforementioned
clinical
that
paved
way
for
approvals.
iScience,
Journal Year:
2024,
Volume and Issue:
27(2), P. 108984 - 108984
Published: Jan. 20, 2024
Olaparib
is
a
pioneering
PARP
inhibitor
(PARPi)
approved
for
treating
castration-resistant
prostate
cancer
(CRPC)
tumors
harboring
DNA
repair
defects,
but
clinical
resistance
has
been
documented.
To
study
acquired
resistance,
we
developed
Olaparib-resistant
(OlapR)
cell
lines
through
chronic
treatment
of
LNCaP
and
C4-2B
lines.
Here,
found
that
IGFBP3
highly
expressed
in
intrinsic
(Rv1)
models
resistance.
We
show
expression
promotes
by
enhancing
capacity
activation
EGFR
DNA-PKcs.
depletion
enhances
efficacy
promoting
damage
accumulation
subsequently,
death
resistant
models.
Mechanistically,
silencing
or
reduces
viability
resensitizes
OlapR
cells
to
treatment.
Inhibition
Gefitinib
suppressed
growth
improved
sensitivity,
thereby
phenocopying
inhibition.
Collectively,
our
results
highlight
as
critical
mediators
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(14), P. 7791 - 7791
Published: July 16, 2024
Combined
gene
and
cell
therapy
are
promising
strategies
for
cancer
treatment.
Given
the
complexity
of
cancer,
several
approaches
actively
studied
to
fight
this
disease.
Using
mesenchymal
stem
cells
(MSCs)
has
demonstrated
dual
antitumor
protumor
effects
as
they
exert
massive
immune/regulatory
on
tissue
microenvironment.
MSCs
have
been
widely
investigated
exploit
their
target
delivery
system.
They
can
be
genetically
modified
overexpress
genes
selectively
or
more
efficiently
eliminate
tumor
cells.
Current
tend
produce
effective
safer
therapies
using
derivatives;
however,
effect
achieved
by
engineered
in
solid
tumors
is
still
limited
depends
factors
such
source,
transgene,
target.
This
review
describes
progress
focused
a
cornerstone
against
tumors,
addressing
different
MSC-engineering
methods
that
approached
over
decades
research.
Furthermore,
we
summarize
main
objectives
most
common
cancers
discuss
challenges,
limitations,
risks,
advantages
targeted
treatments
combined
with
conventional
ones.
Future Oncology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 15
Published: March 19, 2025
Aim
This
study
described
treatment
patterns,
reasons
for
treatment,
and
homologous
recombination
repair
mutation
(HRRm)
testing
patterns
in
a
real-world
metastatic
castration-resistant
prostate
cancer
(mCRPC)
population
Europe.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(16), P. 9032 - 9032
Published: Aug. 20, 2024
Poly
(ADP-Ribose)
Polymerase
(PARP)
inhibitors
have
changed
the
outcomes
and
therapeutic
strategy
for
several
cancer
types.
As
a
targeted
mainly
patients
with
