BackgroundSynthetic
lethality
(SL)
denotes
a
genetic
interaction
between
two
genes
whose
co-inactivation
is
detrimental
to
cells.
Because
more
than
25
years
have
passed
since
SL
was
proposed
as
promising
way
selectively
target
cancer
vulnerabilities,
it
timely
comprehensively
assess
its
impact
so
far
and
discuss
future.MethodsWe
systematically
analyzed
the
literature
clinical
trial
data
from
PubMed
Trialtrove
databases
portray
preclinical
landscape
of
oncology.FindingsWe
identified
235
preclinically
validated
pairs
found
1,207
pertinent
trials,
number
keeps
increasing
over
time.
About
one-third
these
trials
go
beyond
typically
studied
DNA
damage
response
(DDR)
pathway,
testifying
recently
broadening
scope
applications
in
oncology.
We
find
that
oncology
greater
success
rate
non-SL-based
trials.
However,
about
75%
interactions
not
yet
been
tested
trials.ConclusionsDissecting
recent
efforts
harnessing
identify
predictive
biomarkers,
novel
therapeutic
targets,
effective
combination
therapy,
our
systematic
analysis
reinforces
hope
may
serve
key
driver
precision
going
forward.FundingFunded
by
Samsung
Research
Funding
&
Incubation
Center
Electronics,
Institute
Information
Communications
Technology
Planning
Evaluation
(IITP)
grant
funded
Republic
Korea
government
(MSIT),
Kwanjeong
Educational
Foundation,
Intramural
Program
National
Institutes
Health
(NIH),
Cancer
(NCI),
for
(CCR).
Experimental & Molecular Medicine,
Год журнала:
2022,
Номер
54(10), С. 1658 - 1669
Опубликована: Окт. 7, 2022
Abstract
Antitumor
therapeutic
strategies
that
fundamentally
rely
on
the
induction
of
DNA
damage
to
eradicate
and
inhibit
growth
cancer
cells
are
integral
approaches
therapy.
Although
DNA-damaging
therapies
advance
battle
with
cancer,
resistance,
recurrence
following
treatment
common.
Thus,
searching
for
vulnerabilities
facilitate
action
agents
by
sensitizing
is
an
active
research
area.
Therefore,
it
crucial
decipher
detailed
molecular
events
involved
in
responses
(DDRs)
cancer.
The
tumor
suppressor
p53
at
hub
DDR.
Researchers
have
identified
increasing
number
genes
regulated
transcriptional
functions
been
shown
be
critical
direct
or
indirect
mediators
cell
fate,
cycle
regulation,
repair.
Posttranslational
modifications
(PTMs)
primarily
orchestrate
activity
response
damage.
Many
molecules
mediating
PTMs
identified.
anticancer
potential
realized
targeting
these
has
through
experiments
clinical
trials
sensitize
agents.
This
review
briefly
acknowledges
complexity
DDR
pathways/networks.
We
specifically
focus
regulators,
protein
kinases,
E3/E4
ubiquitin
ligases
their
potential.
Cancers,
Год журнала:
2023,
Номер
15(4), С. 1320 - 1320
Опубликована: Фев. 19, 2023
Breast
cancer
is
the
most
common
cause
of
cancer-related
death
in
women
worldwide.
Multidrug
resistance
(MDR)
has
been
a
large
hurdle
reducing
BC
rates.
The
drug
mechanisms
include
increased
efflux,
enhanced
DNA
repair,
senescence
escape,
epigenetic
alterations,
tumor
heterogeneity,
microenvironment
(TME),
and
epithelial-to-mesenchymal
transition
(EMT),
which
make
it
challenging
to
overcome.
This
review
aims
explain
further,
identify
viable
targets,
elucidate
how
those
targets
relate
progression
resistance.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Окт. 18, 2024
Immunotherapy
has
made
significant
strides
in
cancer
treatment,
particularly
through
immune
checkpoint
blockade
(ICB),
which
shown
notable
clinical
benefits
across
various
tumor
types.
Despite
the
transformative
impact
of
ICB
treatment
therapy,
only
a
minority
patients
exhibit
positive
response
to
it.
In
with
solid
tumors,
those
who
respond
well
typically
demonstrate
an
active
profile
referred
as
"hot"
(immune-inflamed)
phenotype.
On
other
hand,
non-responsive
may
distinct
"cold"
(immune-desert)
phenotype,
differing
from
features
tumors.
Additionally,
there
is
more
nuanced
"excluded"
positioned
between
and
categories,
known
type.
Effective
differentiation
understanding
intrinsic
factors,
characteristics,
TME,
external
factors
are
critical
for
predicting
results.
It
widely
accepted
that
therapy
exerts
profound
effect
on
limited
efficacy
against
or
"altered"
necessitating
combinations
therapeutic
modalities
enhance
cell
infiltration
into
tissue
convert
tumors
ones.
Therefore,
aligning
traits
this
review
systematically
delineates
respective
influencing
extensively
discusses
varied
approaches
drug
targets
based
assess
efficacy.
Cancers,
Год журнала:
2024,
Номер
16(13), С. 2478 - 2478
Опубликована: Июль 7, 2024
The
rise
of
drug
resistance
in
cancer
cells
presents
a
formidable
challenge
modern
oncology,
necessitating
the
exploration
innovative
therapeutic
strategies.
This
review
investigates
latest
advancements
overcoming
mechanisms
employed
by
cells,
focusing
on
emerging
modalities.
intricate
molecular
insights
into
resistance,
including
genetic
mutations,
efflux
pumps,
altered
signaling
pathways,
and
microenvironmental
influences,
are
discussed.
Furthermore,
promising
avenues
offered
targeted
therapies,
combination
treatments,
immunotherapies,
precision
medicine
approaches
highlighted.
Specifically,
synergistic
effects
combining
traditional
cytotoxic
agents
with
molecularly
inhibitors
to
circumvent
pathways
examined.
Additionally,
evolving
landscape
immunotherapeutic
interventions,
immune
checkpoint
adoptive
cell
is
explored
terms
bolstering
anti-tumor
responses
evasion
mechanisms.
Moreover,
significance
biomarker-driven
strategies
for
predicting
monitoring
treatment
underscored,
thereby
optimizing
outcomes.
For
future
direction
paradigms,
current
focused
prevailing
challenges
improving
patient
outcomes,
through
an
integrative
analysis
these
Journal of Drug Delivery Science and Technology,
Год журнала:
2024,
Номер
93, С. 105401 - 105401
Опубликована: Янв. 25, 2024
Cancer
is
a
major
public
health
concern
worldwide;
it
the
second-highest
cause
of
death
in
United
States.
According
to
projections
cancer
incidence
and
mortality
rates
throughout
world
for
year
2023,
triple-negative
breast
(TNBC)
expected
be
leading
related
among
women
worldwide.
Traditional
strategies
treatment
TNBC
have
many
drawbacks,
such
as
drug
resistance,
toxicity
etc.
Discovering
novel
delivery
techniques
researching
innovative,
efficient
methods
important.
This
review
discusses
types
subtypes
TNBC.
The
problems
associated
with
standard
therapies,
mechanism
resistance
highlights
need
develop
therapeutic
strategies.
It
provides
information
on
relative
prevalence
severity
cancer.
Several
approaches
viz.
targeted
therapy,
gene
bacterial-mediated
nanomedicine,
immune
checkpoint
inhibitors,
theranostic,
radiotherapy,
chemotherapy,
immunotherapy,
herbal
AI-based
TNBC,
are
discussed
detail.
Additionally,
diagnostic
techniques,
including
imaging
biopsy,
expression
profiling,
mammography,
magnetic
resonance
imaging,
ultrasound,
computed
tomography
scan,
positron
emission
immunohistochemistry,
been
effective
treatment.
in-depth
analysis
innovative
individualized
care
serve
patients
better.
Frontiers in Oncology,
Год журнала:
2024,
Номер
14
Опубликована: Март 8, 2024
About
50%
of
High
Grade
Serous
Ovarian
Cancer
exhibit
a
high
degree
genomic
instability
due
to
mutation
genes
involved
in
Homologous
Recombination
(HRD)
and
such
defect
accounts
for
synthetic
lethality
mechanism
PARP
inhibitors
(PARP-i).
Several
clinical
trials
have
shown
how
BRCA
HRD
mutational
status
profoundly
affect
first
line
chemotherapy
as
well
response
maintenance
therapy
with
PARP-i,
hence
Progression
Free
Survival
Overall
Survival.
Consequently,
there
is
urgent
need
the
development
increasingly
reliable
tests,
overcoming
present
limitations,
they
play
key
role
diagnostic
therapeutic
process
prognostic
predictive
value.
In
this
review
we
offer
an
overview
state
art
regarding
actual
knowledge
about
status,
rationale
PARPi
use
testing
(current
assays)
their
implications
practice
treatment
decision
process,
order
optimize
choose
best
tailored
patients
ovarian
cancer.
