Biomarker Research,
Год журнала:
2024,
Номер
12(1)
Опубликована: Сен. 27, 2024
Abstract
DNA
damage
response
(DDR)
deficiency
has
been
one
of
the
emerging
targets
in
treating
breast
cancer
recent
years.
On
hand,
DDR
coordinates
cell
cycle
and
signal
transduction,
whose
dysfunction
may
lead
to
apoptosis,
genomic
instability,
tumor
development.
Conversely,
is
an
intrinsic
feature
tumors
that
underlies
their
treatments
inflict
damage.
In
this
review,
we
systematically
explore
various
mechanisms
DDR,
rationale
research
advances
DDR-targeted
drugs
cancer,
discuss
challenges
its
clinical
applications.
Notably,
poly
(ADP-ribose)
polymerase
(PARP)
inhibitors
have
demonstrated
favorable
efficacy
safety
with
high
homogenous
recombination
(HRD)
status
a
series
trials.
Moreover,
several
studies
on
novel
DDR-related
molecules
are
actively
exploring
target
become
resistant
PARP
inhibition.
Before
further
application
new
regimens
or
drugs,
standardized
biomarkers
needed
develop
for
accurately
characterizing
benefit
population
predicting
efficacy.
Despite
promising
treatments,
off-target
toxicity
drug
resistance
need
be
addressed.
Strategies
overcome
await
exploration
mechanisms,
combined
targeted
immunotherapy
will
hopefully
provide
more
precise
strategies
expand
potential
responsive
populations.
Toxicology Mechanisms and Methods,
Год журнала:
2021,
Номер
32(6), С. 395 - 419
Опубликована: Дек. 21, 2021
Aflatoxins
are
a
class
of
carcinogenic
mycotoxins
produced
by
Aspergillus
fungi,
which
widely
distributed
in
nature.
Aflatoxin
B1
(AFB1)
is
the
most
toxic
these
compounds
and
its
metabolites
have
variety
biological
activities,
including
acute
toxicity,
teratogenicity,
mutagenicity
carcinogenicity,
has
been
well-characterized
to
lead
development
hepatocellular
carcinoma
(HCC)
humans
animals.
This
review
focuses
on
metabolism
AFB1,
epoxidation
DNA
adduction,
as
it
concerns
initiation
cancer
underlying
mechanisms.
In
addition
inflammation
oxidative
stress
caused
AFB1
can
also
participate
occurrence
cancer.
Therefore,
main
mechanism
related
ROS
summarized.
describes
recent
reports
exposures
occupational
settings.
It
hoped
that
people
will
pay
more
attention
health,
order
reduce
incidence
exposure.
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.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(2), С. 1263 - 1263
Опубликована: Янв. 19, 2024
Replication
stress
(RS)
is
a
characteristic
state
of
cancer
cells
as
they
tend
to
exchange
precision
replication
for
fast
proliferation
and
increased
genomic
instability.
To
overcome
the
consequences
improper
control,
malignant
frequently
inactivate
parts
their
DNA
damage
response
(DDR)
pathways
(the
ATM-CHK2-p53
pathway),
while
relying
on
other
which
help
maintain
fork
stability
(ATR-CHK1).
This
creates
dependency
remaining
DDR
pathways,
vulnerability
further
destabilization
synthetic
lethality
inhibitors
with
common
oncogenic
alterations
such
mutations
TP53,
RB1,
ATM,
amplifications
MYC,
CCNE1
others.
The
RS
normally
limited
by
coordination
cell
cycle,
transcription
replication.
Inhibition
WEE1
PKMYT1
kinases,
prevent
unscheduled
mitosis
entry,
leads
fragility
under-replicated
sites.
Recent
evidence
also
shows
that
inhibition
Cyclin-dependent
kinases
(CDKs),
CDK4/6,
CDK2,
CDK8/19
CDK12/13
can
contribute
through
disruption
repair
control.
Here,
we
review
main
causes
in
cancers
well
therapeutic
targets—ATR,
CHK1,
PARP
inhibitors.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Янв. 12, 2025
Abstract
Cyclin
Dependent
Kinases
(CDKs)
are
closely
connected
to
the
regulation
of
cell
cycle
progression,
having
been
first
identified
as
kinases
able
drive
division.
In
reality,
human
genome
contains
20
different
CDKs,
which
can
be
divided
in
at
least
three
sub-family
with
functions,
mechanisms
regulation,
expression
patterns
and
subcellular
localization.
Most
these
play
fundamental
roles
normal
physiology
eucaryotic
cells;
therefore,
their
deregulation
is
associated
onset
and/or
progression
multiple
disease
including
but
not
limited
neoplastic
neurodegenerative
conditions.
Here,
we
describe
functions
categorized
into
main
functional
groups
they
classified,
highlighting
most
relevant
pathways
that
functions.
We
then
discuss
potential
CDKs
pathologies,
a
particular
focus
on
cancer,
have
extensively
studied
explored
therapeutic
targets.
Finally,
how
inhibitors
become
standard
therapies
selected
cancers
propose
novel
ways
investigation
export
targeting
from
cancer
other
chronic
diseases.
hope
effort
made
collecting
all
available
information
both
prominent
lesser-known
CDK
family
members
will
help
identify
develop
areas
research
improve
lives
patients
affected
by
debilitating
Biochemical Society Transactions,
Год журнала:
2023,
Номер
51(1), С. 207 - 221
Опубликована: Янв. 6, 2023
The
DNA
damage
response
(DDR)
is
an
elegant
system,
coordinating
repair
with
cell
cycle
checkpoints,
that
evolved
to
protect
living
organisms
from
the
otherwise
fatal
levels
of
inflicted
by
endogenous
and
environmental
sources.
Since
many
agents
used
treat
cancer;
radiotherapy
cytotoxic
chemotherapy,
work
damaging
DDR
represents
a
mechanism
resistance.
original
rational
for
development
drugs
inhibit
was
overcome
this
resistance
but
clinical
studies
using
approach
have
not
led
improvements
in
therapeutic
index.
A
more
exciting
exploit
cancer-specific
defects
DDR,
represent
vulnerabilities
tumour
opportunity
selectively
target
tumour.
PARP
inhibitors
(PARPi)
kill
homologous
recombination
defective
(HRD,
e.g.
through
BRCA
mutation)
cells.
This
has
proven
successful
clinically
there
are
now
six
PARPi
approved
cancer
therapy.
Drugs
targeting
other
aspects
under
pre-clinical
evaluation
as
monotherapy
combination
studies.
For
promising
therapy
be
fully
realised
reliable
biomarkers
needed
identify
tumours
exploitable
defect
applications.
possibility
some
combinations
may
result
toxicity
normal
tissues
also
needs
considered.
brief
overview
current
status
such
described
here.
Journal of Cancer Research and Clinical Oncology,
Год журнала:
2024,
Номер
150(1)
Опубликована: Янв. 1, 2024
Abstract
Purpose
WEE1
is
a
crucial
kinase
involved
in
the
regulation
of
G2/M
checkpoint
within
cell
cycle.
This
article
aims
to
comprehensively
review
existing
knowledge
on
implication
as
therapeutic
target
tumor
progression
and
drug
resistance.
Furthermore,
we
summarize
current
predictive
biomarkers
employed
treat
cancer
with
inhibitors.
Methods
A
systematic
literature
was
conducted
analyze
association
between
inhibition
progression,
including
advancement
Special
attention
paid
identification
utilization
related
response
Results
The
highlights
intricate
involvement
It
synthesizes
inhibitor
treatments,
offering
insights
into
their
prognostic
significance.
Notably,
elucidates
potential
for
precision
medicine
by
understanding
these
context
treatment
outcomes.
Conclusion
plays
pivotal
role
promising
target.
Distinguishing
patients
that
would
benefit
from
will
be
major
direction
future
research.
