Recent Advances in the Clinical Translation of Small-Cell Lung Cancer Therapeutics
Cancers,
Год журнала:
2025,
Номер
17(2), С. 255 - 255
Опубликована: Янв. 14, 2025
Small-cell
lung
cancer
(SCLC)
is
a
recalcitrant
form
of
cancer,
representing
15%
cases
globally.
SCLC
classified
within
the
range
neuroendocrine
pulmonary
neoplasms,
exhibiting
shared
morphologic,
ultrastructural,
immunohistochemical,
and
molecular
genomic
features.
It
marked
by
rapid
proliferation,
propensity
for
early
metastasis,
an
overall
poor
prognosis.
The
current
conventional
therapies
involve
platinum–etoposide-based
chemotherapy
in
combination
with
immunotherapy.
Nonetheless,
emergence
therapeutic
resistance
continues
to
pose
substantial
difficulties.
profiling
uncovers
significant
chromosomal
rearrangements
along
considerable
mutation
burden,
typically
involving
functional
inactivation
tumor
suppressor
genes
TP53
RB1.
Identifying
biomarkers
evaluating
new
treatments
crucial
enhancing
outcomes
patients
SCLC.
Targeted
such
as
topoisomerase
inhibitors,
DLL3
HDAC
PARP
Chk1
etc.,
have
introduced
options
future
applications.
In
this
review,
we
will
attempt
outline
key
pathways
that
play
role
development
progression
SCLC,
together
comprehensive
overview
most
recent
advancements
novel
targeted
treatment
strategies,
well
some
ongoing
clinical
trials
against
goal
improving
patient
outcomes.
Язык: Английский
Noncanonical inhibition of topoisomerase II alpha by oxidative stress metabolites
Redox Biology,
Год журнала:
2025,
Номер
unknown, С. 103504 - 103504
Опубликована: Янв. 1, 2025
During
its
catalytic
cycle,
the
homodimeric
ATPase
topoisomerase
II
alpha
(TOP2A)
cleaves
double
stranded
DNA
and
remains
covalently
bound
to
5'
ends
via
tyrosine
phosphodiester
bonds.
After
passing
a
second,
intact
duplex
through,
TOP2A
rejoins
break
releases
from
DNA.
Thereby,
can
relieve
strain
accumulated
during
transcription,
replication
chromatin
remodeling
disentangle
sister
chromatids
for
mitosis.
Chemotherapy
agents
such
as
etoposide
are
poisons
that
trap
mid-cycle,
cleaved
DNA,
leaving
behind
strand
breaks
activating
damage
response.
While
has
been
proposed
stabilize
TOP2A-DNA
cleavage
complex
(TOP2Acc)
interfacial
inhibition,
we
have
elucidated
complementary
mechanism
mediated
by
ability
of
other
induce
oxidative
stress.
Consequently,
lipid
peroxidation
accumulation
lipid-derived
electrophiles
4-hydroxynonenal
(HNE)
results
in
covalent
modification
TOP2A,
both
blocking
activity
trapping
TOP2Acc.
HNE
modifies
multiple
sites
on
human
vitro,
including
alkylating
Cys216
domain
DNA-dependent
fashion.
Taken
together,
our
data
suggest
an
underappreciated
role
redox
sensor
tumor
cells,
connecting
stress
signaling
thereby
creating
target
redox-active
drugs.
Язык: Английский
Synthesis, Structural Modification, and Antismall Cell Lung Cancer Activity of 3-Arylisoquinolines with Dual Inhibitory Activity on Topoisomerase I and II
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 22, 2025
To
overcome
the
compensatory
effect
between
Topo
I
and
II,
one
of
reasons
accounting
for
resistance
SCLC
patients,
we
are
pioneering
use
3-arylisoquinolines
to
develop
dual
inhibitors
I/II
management
SCLC.
A
total
46
new
compounds
were
synthesized.
Compounds
3g
(IC50
=
1.30
μM
NCI-H446
cells
1.42
NCI-H1048
cells)
3x
1.32
2.45
selected
detailed
pharmacological
investigation,
due
their
outstanding
cytotoxicity
II
inhibitory
activity.
effectively
prevent
cell
proliferation,
invasion,
migration
in
vitro,
byinducing
mitochondrial
apoptosis
inhibiting
PI3K/Akt/mTOR
pathway.
Their
vivo
tumor
inhibition
rate
is
comparable
etoposide
with
lower
toxicity.
These
results
indicated
potential
therapeutic
values
as
treating
Язык: Английский
Identification of Promising Lung Cancer Drug Targets from Human Plasma Proteins: Mendelian Randomization,Single-Cell Rna Sequencing Analysis
Опубликована: Янв. 1, 2025
Язык: Английский
Treatment Advances in Small Cell Lung Cancer
Advances in Oncology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Язык: Английский
An Overview of the Bioactivity of Spontaneous Medicinal Plants Suitable for the Improvement of Lung Cancer Therapies
Pharmaceutics,
Год журнала:
2025,
Номер
17(3), С. 336 - 336
Опубликована: Март 5, 2025
Lung
cancer
is
the
second
cause
of
death
in
world,
being
most
common
type
cancer.
Conventional
therapies
are
not
always
recommended
due
to
particularities
patients.
Thus,
there
a
need
develop
new
anticancer
therapeutic
agents.
Medicinal
plants
constitute
source
bioactive
compounds
with
potential
lung
The
purpose
our
narrative
review
evaluate
and
summarize
main
studies
on
cytotoxic
effects
ten
medicinal
their
extracts,
volatile
oils,
compounds.
We
have
also
included
that
reported
protective
these
natural
products
against
chemotherapy-induced
toxicity.
Studies
were
identified
by
assessing
five
databases
using
specific
keywords.
investigated
possess
cell
cultures.
Several
mechanisms
action
been
proposed
including
apoptosis,
necrosis
or
autophagy,
cycle
arrest,
modulation
signaling
pathways
(PI3K/Akt
MAPK),
inhibition
migration,
invasion
metastasis,
antiangiogenesis,
targeting
inflammation.
Different
exhibit
shown
promising
results.
To
agents
useful
treating
cancer,
this
should
be
more
deeply
reveal
molecular
action.
Язык: Английский
Circular RNAs modulate cancer drug resistance: advances and challenges
Cancer Drug Resistance,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 28, 2025
Acquired
drug
resistance
is
a
main
factor
contributing
to
cancer
therapy
failure
and
high
mortality,
highlighting
the
necessity
develop
novel
intervention
targets.
Circular
RNAs
(circRNAs),
an
abundant
class
of
RNA
molecules
with
closed
loop
structure,
possess
characteristics
including
stability,
which
provide
unique
advantages
in
clinical
application.
Growing
evidence
indicates
that
aberrantly
expressed
circRNAs
are
associated
against
various
treatments,
targeted
therapy,
chemotherapy,
radiotherapy,
immunotherapy.
Therefore,
targeting
these
aberrant
may
offer
strategy
improve
efficiency
therapy.
Herein,
we
present
summary
most
recently
studied
their
regulatory
roles
on
resistance.
With
advances
artificial
intelligence
(AI)-based
bioinformatics
algorithms,
could
emerge
as
promising
biomarkers
targets
Язык: Английский
Mechanism of etoposide resistance in small cell lung cancer and the potential therapeutic options
Medical Oncology,
Год журнала:
2025,
Номер
42(5)
Опубликована: Апрель 21, 2025
Язык: Английский
MiRNAs function in the development of resistance against doxorubicin in cancer cells: targeting ABC transporters
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 29, 2024
Resistance
to
chemotherapeutic
agents
poses
a
significant
challenge
in
cancer
treatment,
particularly
with
doxorubicin,
widely
used
drug
for
various
cancers,
including
breast
cancer,
leukaemia,
osteosarcoma,
and
gastrointestinal
cancers.
This
review
aims
elucidate
the
critical
role
of
microRNAs
(miRNAs)
development
doxorubicin
resistance,
focusing
on
their
interactions
ATP-binding
cassette
(ABC)
transporters.
Despite
extensive
research,
molecular
mechanisms
governing
resistance
still
need
be
completed,
regarding
regulatory
influence
miRNAs
ABC
transporter
expression.
By
analyzing
current
literature,
this
identifies
notable
gap:
lack
comprehensive
insight
into
how
specific
modulate
expression
activity
transporters
cells,
contributing
resistance.
We
systematically
examine
recent
findings
interplay
between
transporters,
providing
detailed
assessment
potential
therapeutic
strategies
that
leverage
miRNA
modulation
overcome
Ultimately,
underscores
significance
integrating
research
existing
frameworks
enhance
efficacy
treatment.
Язык: Английский