Cells,
Journal Year:
2023,
Volume and Issue:
12(15), P. 1929 - 1929
Published: July 25, 2023
MAGI1
acts
as
a
tumor
suppressor
in
estrogen
receptor-positive
(ER+)
breast
cancer
(BC),
and
its
loss
correlates
with
more
aggressive
phenotype.
To
identify
the
pathways
events
affected
by
loss,
we
deleted
gene
ER+
MCF7
BC
cell
line
performed
RNA
sequencing
functional
experiments
vitro.
Transcriptome
analyses
revealed
sets
biological
processes
related
to
signaling,
cycle,
DNA
damage
responses
loss.
Upon
exposure
TNF-α/IFN-γ,
KO
cells
entered
deeper
level
of
quiescence/senescence
compared
control
activated
AKT
MAPK
signaling
pathways.
exposed
ionizing
radiations
or
cisplatin
had
reduced
expression
repair
proteins
showed
increased
sensitivity
towards
PARP1
inhibition
using
olaparib.
Treatment
PI3K
inhibitors
(alpelisib
MK-2206)
restored
sensitized
fulvestrant.
An
analysis
human
patients’
transcriptomic
data
that
patients
low
levels
higher
mutational
burden
homologous
recombination
deficiency.
Moreover,
negatively
correlated
PI3K/AKT
which
confirmed
our
vitro
observations.
Pharmacological
genomic
evidence
indicate
HDACs
regulators
expression.
Our
findings
provide
new
view
on
function
potential
treatment
options
improve
management
levels.
Diagnostics,
Journal Year:
2023,
Volume and Issue:
13(11), P. 1896 - 1896
Published: May 29, 2023
The
Homologous
Recombination
Deficiency
(HRD)
Score,
determined
by
evaluating
genomic
instability
through
the
assessment
of
loss
heterozygosity
(LOH),
telomeric
allelic
imbalance
(TAI),
and
large-scale
state
transitions
(LST),
serves
as
a
crucial
biomarker
for
identifying
patients
who
might
benefit
from
targeted
therapies,
such
PARP
inhibitors
(PARPi).
This
study
aimed
to
investigate
efficacy
HRD
testing
in
high-grade
serous
ovarian
carcinoma,
tubal,
peritoneal
cancer
are
negative
somatic
BRCA1
BRCA2
mutations
evaluate
impact
status
on
Bevacizumab
PARPi
therapy
response.
A
cohort
100
Romanian
female
patients,
aged
42–77,
was
initially
selected.
Among
them,
30
had
unsuitable
samples
due
insufficient
tumor
content
or
DNA
integrity.
Using
OncoScan
C.N.V.
platform,
successfully
performed
remaining
70
with
20
50
positive
HRD.
HRD-positive
35
were
eligible
benefited
maintenance
therapy,
resulting
median
progression-free
survival
(PFS)
increase
4
months
8.2
months.
Our
findings
support
importance
demonstrating
potential
therapeutic
advantage
without
BRCA1/2
mutations.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: June 25, 2024
Standard
therapy
for
high-grade
ovarian
carcinoma
includes
surgery
followed
by
platinum-based
chemotherapy
and
poly-ADP
ribose
polymerase
inhibitors
(PARPis).
Deficiency
in
homologous
recombination
repair
(HRD)
characterizes
almost
half
of
carcinomas
is
due
to
genetic
epigenetic
alterations
genes
involved
HR
repair,
mainly
BRCA1/BRCA2,
predicts
response
PARPi.
The
academic
commercial
tests
set
up
define
the
HRD
status
tumor
rely
on
DNA
sequencing
analysis,
while
functional
such
as
RAD51
foci
assay
are
currently
under
study,
but
have
not
been
validated
yet
available
patients.
In
a
well-characterized
patient-derived
xenograft
platform
whose
cisplatin
olaparib,
PARPi,
known,
we
assessed
association
between
BRCA1
score,
determined
formalin-fixed
paraffin-embedded
slices
with
an
immunofluorescence
technique,
other
biomarkers
explored
potential
test
predict
tumors’
olaparib.
score
was
associated
both
score.
A
low
predicted
olaparib
cisplatin,
high
resistance
therapy.
As
recently
published
that
sensitivity
our
xenobank,
combined
two
scores
showed
predictive
value
better
than
single
tests.
This
study
reports
first
time
capacity
identify
possibly
Cureus,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 2, 2024
Poly(adenosine
diphosphate
ribose)
polymerase
(PARP)
inhibitors
have
appeared
as
a
revolutionary
approach
to
treating
advanced
ovarian
cancer,
particularly
in
patients
with
breast
cancer
(BRCA)
mutations
and
homologous
recombination
deficiency
(HRD).
This
narrative
review
explores
PARP
inhibitors'
clinical
efficiency,
safety,
changing
role
this
context.
inhibitors,
such
olaparib,
niraparib,
or
rucaparib,
provide
considerable
benefits
regarding
progression-free
survival
expansion
overall
outcomes
improvement
first-line
maintenance
recurrent
settings.
The
underlying
mechanisms,
patient
selection
criteria,
resistance
patterns
are
discussed,
alongside
insights
into
combination
therapies
overcome
enhance
therapeutic
efficacy.
Ongoing
trials
future
potential
for
personalized
therapy
approaches
using
also
highlighted.
However,
despite
these
drugs'
phenomenal
ability
revolutionize
treatment
protocols
types,
several
challenges
remain:
toxicity
management,
cost,
development
of
will
require
more
research
optimize
their
use
broaden
populations
who
can
benefit
from
them.
Revista da Associação Médica Brasileira,
Journal Year:
2024,
Volume and Issue:
70(10)
Published: Sept. 30, 2024
The
objective
of
this
study
was
to
analyze
the
genetic
alterations
tumors
within
scope
homologous
recombination
deficiency
gene
panel
in
patients
diagnosed
with
synchronous
endometrial
ovarian
cancer
who
have
been
followed
for
over
5
years
using
next-generation
sequencing.
npj Precision Oncology,
Journal Year:
2024,
Volume and Issue:
8(1)
Published: Oct. 14, 2024
The
synthetic
lethal
effect
observed
with
the
use
of
PARP
inhibitors
(PARPi)
tumors
characterized
by
loss
key
players
in
homologous
recombination
(HR)
pathway,
commonly
referred
to
as
"BRCAness",
is
maintaining
high
interest
oncology.
While
BRCAness
a
well-established
feature
breast,
ovarian,
prostate,
and
pancreatic
carcinomas,
our
recent
findings
indicate
that
up
15%
colorectal
cancers
(CRC)
also
harbor
defects
HR
presenting
promising
opportunities
for
innovative
therapeutic
strategies
CRC
patients.
We
developed
new
tool
called
HRDirect,
which
builds
upon
HRDetect
algorithm
able
predict
deficiency
(HRD)
from
reference-free
tumor
samples.
validated
HRDirect
using
matched
breast
cancer
patient
Subsequently,
we
assessed
its
efficacy
predicting
response
inhibitor
olaparib
comparing
it
two
other
commercial
assays:
AmoyDx
HRD
Amoy
Diagnostics
TruSight
Oncology
500
(TSO500-HRD)
panel
Illumina
NGS
technology.
all
three
approaches
successfully
identified
most
PARPi-sensitive
models,
demonstrated
superior
precision
distinguishing
resistant
models
compared
AmoyDX
TSO500-HRD,
exhibited
overlapping
scores
between
sensitive
cells.
Furthermore,
propose
integrating
scoring
ATM
RAD51C
immunohistochemical
analysis
part
"composite
biomarker
approach"
enhance
identification
tumors,
an
immediate
translational
clinical
impact
personalized
treatment.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(22), P. 3728 - 3728
Published: Nov. 5, 2024
Clinical
use
of
poly(ADP-ribose)
polymerase
inhibitors
(PARPis)
against
metastatic
high-grade
serous
ovarian
carcinoma
(HGSOC)
is
limited
to
cases
with
deficient
a
homologous
recombination
(HR).
Our
objective
was
determine
whether
the
impairment
fractalkine
receptor
(CX
Frontiers in Oncology,
Journal Year:
2024,
Volume and Issue:
14
Published: Nov. 6, 2024
The
discovery
of
gene
fusions
involving
Neuregulin-1
(
NRG1
)
within
solid
tumors
has
important
therapeutic
implications,
as
they
are
being
actively
explored
targets
for
emerging
ERBB/ERBB2/ERBB3-directed
anti-cancer
agents.
very
uncommon
across
all
tumor
types
and
infrequently
documented
in
the
medical
literature.
We
report
a
female
patient
presenting
with
widespread
peritoneal
carcinomatosis
diagnosed
high
grade
serous
fallopian
tube
carcinoma,
which
harbored
previously
undescribed
MYH10
::
fusion.
Moreover,
we
queried
whole
transcriptome
sequencing
results
neoplasms
analyzed
by
commercial
laboratory
(Caris
Life
Sciences)
to
determine
overall
incidence
carcinomas
ovary,
tube,
peritoneum
(0.18%).
Twenty-five
additional
were
found
demonstrate
fusions,
including
20
new
genes
partners
that
had
not
been
identified
gynecologic
carcinomas.
Overall,
fusion
events
rare
ovarian,
primary
carcinomas,
but
may
carry
diagnostic
significance
context
borderline/low
tumors,
demonstrated
exclusively
CLU::NRG1
could
have
predictive
implications
response
therapies.
Cells,
Journal Year:
2023,
Volume and Issue:
12(15), P. 1929 - 1929
Published: July 25, 2023
MAGI1
acts
as
a
tumor
suppressor
in
estrogen
receptor-positive
(ER+)
breast
cancer
(BC),
and
its
loss
correlates
with
more
aggressive
phenotype.
To
identify
the
pathways
events
affected
by
loss,
we
deleted
gene
ER+
MCF7
BC
cell
line
performed
RNA
sequencing
functional
experiments
vitro.
Transcriptome
analyses
revealed
sets
biological
processes
related
to
signaling,
cycle,
DNA
damage
responses
loss.
Upon
exposure
TNF-α/IFN-γ,
KO
cells
entered
deeper
level
of
quiescence/senescence
compared
control
activated
AKT
MAPK
signaling
pathways.
exposed
ionizing
radiations
or
cisplatin
had
reduced
expression
repair
proteins
showed
increased
sensitivity
towards
PARP1
inhibition
using
olaparib.
Treatment
PI3K
inhibitors
(alpelisib
MK-2206)
restored
sensitized
fulvestrant.
An
analysis
human
patients’
transcriptomic
data
that
patients
low
levels
higher
mutational
burden
homologous
recombination
deficiency.
Moreover,
negatively
correlated
PI3K/AKT
which
confirmed
our
vitro
observations.
Pharmacological
genomic
evidence
indicate
HDACs
regulators
expression.
Our
findings
provide
new
view
on
function
potential
treatment
options
improve
management
levels.
