Targeting Metabolic and Epigenetic Vulnerabilities in Glioblastoma with SN-38 and Rabusertib Combination Therapy
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(2), С. 474 - 474
Опубликована: Янв. 8, 2025
Glioblastoma
(GBM),
the
most
prevalent
primary
malignant
brain
tumor,
remains
challenging
to
treat
due
extensive
inter-
and
intra-tumor
heterogeneity.
This
variability
demands
combination
treatments
improve
therapeutic
outcomes.
A
significant
obstacle
in
treating
GBM
is
expression
of
O6-methylguanine-DNA
methyltransferase,
a
DNA
repair
enzyme
that
reduces
efficacy
standard
alkylating
agent,
temozolomide,
about
50%
patients.
underscores
need
for
novel,
more
targeted
therapies.
Our
study
investigates
metabolic-epigenetic
impact
combining
SN-38,
novel
topoisomerase
inhibitor
inducing
double-strand
breaks,
with
rabusertib,
checkpoint
kinase
1
inhibitor.
We
identified
this
synergistic
through
high-throughput
drug
screening
across
panel
cell
lines
using
cancer
library
combined
SN-38.
secondary
metabolic
PEDS
algorithm
demonstrated
modulation
purine,
one-carbon,
redox
metabolism.
Furthermore,
treatment
led
depletion
epigenetically
relevant
metabolites
such
as
5-methyl-cytosine,
acetyl-lysine,
trimethyl-lysine.
Reduced
intermediates
glutathione
cycle
indicated
increased
cellular
stress
following
combinatorial
treatment.
Overall,
SN-38
rabusertib
synergistically
disrupts
associated
epigenetic
adaptations,
leading
cytotoxicity
independent
methyltransferase
status,
thereby
underpinning
promising
candidate
therapy
GBM.
Язык: Английский
Cost-effectiveness of sacituzumab govitecan for hormone receptor-positive human epidermal growth factor receptor 2-negative metastatic breast cancer based on the EVER-132-002 trial in China
Cost Effectiveness and Resource Allocation,
Год журнала:
2025,
Номер
23(1)
Опубликована: Март 19, 2025
The
EVER-132-002
trial
demonstrated
the
significant
efficacy
and
manageable
safety
of
sacituzumab
govitecan
in
hormone
receptor-positive
human
epidermal
growth
factor
receptor
2-negative
(HR
+
HER2-)
metastatic
breast
cancer.
This
study
evaluated
cost-effectiveness
compared
with
chemotherapy
from
Chinese
healthcare
system
perspective.
A
partitioned
survival
model
at
21-day
intervals
over
a
10-year
time
horizon
was
developed
to
evaluate
total
cost,
quality-adjusted
life-years
(QALYs),
incremental
ratio
(ICER)
willingness-to-pay
(WTP)
threshold
3
times
gross
domestic
product
per
capita
($38,042.49
QALY).
Clinical
data
were
extracted
trial;
direct
medical
costs
utility
values
obtained
public
bid-winning
databases,
local
charges
or
published
literature.
To
determine
model's
robustness,
scenario,
one-way,
two-way
probabilistic
sensitivity
analyses
performed.
Compared
chemotherapy,
generated
an
additional
cost
$91,273.72,
QALY
0.43,
resulted
ICER
$211,948.62
QALY.
Patient
weight
most
influential
parameter
on
base-case
results,
variations
each
did
not
substantially
alter
conclusion.
Probabilistic
analysis
that
probability
be
cost-effective
zero
WTP
$38,042.49
Scenario
indicated
would
versus
only
if
its
reduced
by
83%
($202.65
unit)
more.
Sacituzumab
might
treatment
for
HR
HER2-
cancer
China.
Язык: Английский
Antibody-drug conjugates in breast cancer: current evidence and future directions
Experimental Hematology and Oncology,
Год журнала:
2025,
Номер
14(1)
Опубликована: Март 20, 2025
Abstract
Antibody-drug
conjugates
(ADCs)
are
a
rapidly
evolving
class
of
antitumor
drugs
and
have
already
revolutionized
the
treatment
strategy
many
hematologic
solid
cancers.
So
far,
trastuzumab
emtansine
(T-DM1),
deruxtecan
(T-DXd),
sacituzumab
govitecan
(SG)
datopotamab
(Dato-DXd)
four
ADCs
that
been
approved
by
US
food
drug
administration
(FDA)
in
breast
cancer,
SKB264
has
Chinese
national
medical
products
(NMPA).
Many
for
cancer
currently
being
tested
late-phase
clinical
trials,
with
several
encouraging
results
achieved
recently.
However,
major
issues
arise
during
use
ADCs,
including
emergence
acquired
resistance,
occurrence
treated-related
toxicities,
identification
biomarkers
response
resistance.
increasingly
combination
other
agents,
novel
next-generation
ADC
development
is
progressing
rapidly.
A
better
understanding
design
will
promote
treatment.
In
this
review,
we
aim
to
provide
broad
overview
recent
advances
cancer.
We
also
propose
notable
future
directions
Язык: Английский
Toxicities and management strategies of emerging antibody–drug conjugates in breast cancer
Therapeutic Advances in Medical Oncology,
Год журнала:
2025,
Номер
17
Опубликована: Янв. 1, 2025
Antibody–drug
conjugates
(ADCs)
offer
a
promising
therapeutic
approach
for
various
cancers,
enhancing
the
window
while
mitigating
systemic
adverse
effects
on
healthy
tissues.
ADCs
have
achieved
remarkable
clinical
success,
particularly
in
treating
breast
cancer,
becoming
standard
therapy
across
all
subtypes,
including
hormone
receptor-positive,
human
epidermal
growth
factor
receptor
2-positive,
and
triple-negative
cancer.
Although
designed
to
selectively
target
antigens
via
monoclonal
antibodies,
can
exhibit
toxicity
normal
tissues,
often
due
off-target
of
their
cytotoxic
payloads.
Understanding
managing
these
toxicities
according
established
guidelines
are
crucial
ADC
efficacy,
minimizing
events,
ultimately
improving
patient
outcomes.
This
review
comprehensively
examines
employed
cancer
treatment
explores
management
strategies.
Furthermore,
we
investigate
novel
beyond
trastuzumab
deruxtecan
sacituzumab
govitecan,
evaluating
potential
efficacy
corresponding
safety
profiles.
Язык: Английский