Cancers,
Год журнала:
2024,
Номер
17(1), С. 16 - 16
Опубликована: Дек. 24, 2024
In
hormone
receptor-positive
and
HER2-negative
breast
cancers,
a
growing
number
of
revolutionary
personalized
therapies
are
in
clinical
use
or
trials,
such
as
CDK4/6
inhibitors,
immune
checkpoint
PIK3CA
inhibitors.
Those
treatment
options
largely
driven
by
the
presence
absence
genomic
alterations
tumor.
Therefore,
molecular
profiling
is
often
performed
during
disease
progression.
The
most
encountered
PI3K/AKT/mTOR/PTEN
pathway.
This
review
discusses
genetic
associated
with
pathway
to
help
clinicians
understand
drug
selection,
resistance,
interaction
from
pathologist’s
perspective.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 4, 2025
Cyclin-dependent
kinases
4
and
6
(CDK4/6)
are
central
regulators
of
cell
cycle
progression
frequently
dysregulated
in
cancers,
including
breast
cancer.
While
selective
CDK4/6
inhibitors
like
Palbociclib,
Ribociclib,
Abemaciclib
have
shown
clinical
benefit
hormone
receptor-positive
(HR+)
cancer,
their
efficacy
is
often
limited
by
resistance
mechanisms
dose-limiting
toxicities.
In
this
study,
we
developed
LA-CB1,
a
novel
derivative
that
induces
degradation
through
the
ubiquitin-proteasome
pathway,
aiming
to
achieve
sustained
inhibition
CDK4/6-Rb
axis.
LA-CB1
demonstrated
potent
anti-proliferative
effects
various
cancer
lines,
with
notable
triple-negative
(TNBC)
HR
+
models.
Molecular
docking
studies
confirmed
high-affinity
binding
ATP-binding
pocket
CDK4/6.
Mechanistic
revealed
G0/G1
arrest
promotes
apoptosis
Importantly,
also
suppressed
epithelial-mesenchymal
transition
(EMT),
inhibiting
key
processes
such
as
migration,
invasion,
angiogenesis,
indicating
its
ability
disrupt
multiple
hallmarks
an
orthotopic
model,
significantly
reduced
tumor
growth
dose-dependent
manner.
These
results
suggest
represents
promising
therapeutic
strategy
targeting
for
degradation,
addressing
limitations
associated
current
inhibitors,
providing
broad
anti-tumor
activity
aggressive
types
TNBC.
Breast
cancer
(BC)
patients
face
abnormal
lipid
metabolism
and
increased
cardiovascular
disease
(CVD)
risk
due
to
endocrine
therapies
(ETs).
This
study
evaluates
CVD
incidence
abnormalities
in
Chinese
with
early-stage
hormone
receptor-positive
(HR+)
BC
inform
personalized
treatments.
Data
from
female
aged
18-80
years
stage
I-III
HR
+
registered
the
National
Cancer
Center
Oncology
Information
Database
(NCCOID)
(2013-2018)
were
analyzed.
Outcomes
included
profile
changes,
incidence,
five-year
survival
rates.
Among
11,537
patients,
ETs
significantly
disrupted
metabolism,
increasing
total
cholesterol,
triglycerides,
LDL-C,
HDL-C
levels.
Nonsteroidal
aromatase
inhibitors
(NSAI)
±
ovarian
function
suppression
(OFS)
led
largest
increase
cholesterol
(10.26
17.32%),
while
selective
estrogen
receptor
modulators
(SERM)
OFS
caused
greatest
rises
triglycerides
(16.07
25.86%),
LDL-C
(12.11
23.34%),
(10.86
17.23%).
Only
3.82%
of
received
lipid-lowering
therapy.
associated
higher
including
hypertension,
myocardial
infarction,
atrial
fibrillation,
but
rates
did
not
differ
across
ET
regimens
(P
>
0.05).
may
be
alterations
a
potential
patients.
These
findings
highlight
relevance
enhanced
monitoring
management
support
optimized
treatment
outcomes
population.
RSC Advances,
Год журнала:
2025,
Номер
15(15), С. 11893 - 11901
Опубликована: Янв. 1, 2025
A
novel
nanocatalyst
based
on
Cu/Au-doped
polypyrrole
has
been
synthesized
for
NIR
II
laser-promoted
nanocatalytic
tumor
therapy
through
several
enhanced
catalytic
mechanisms,
including
elevated
temperature
and
electron
migration.
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 15, 2025
Background
Endocrine
therapy
combined
with
CDK4/6
inhibitors
remains
a
standard
treatment
for
ER+
breast
cancer,
yet
resistance
is
prevalent
challenge.
This
study
explores
the
role
of
N6-methyladenosine
(m6A)
modifications,
influenced
by
m6A-SNPs,
in
shaping
resistance,
utilizing
single-cell
RNA
sequencing
to
delineate
underlying
molecular
mechanisms.
Methods
We
integrated
genome-wide
association
data
transcriptomic
profiles
from
cancer
patients,
focusing
on
differences
between
resistant
and
sensitive
responses
inhibitors.
m6A-SNPs
were
identified
analyzed
their
impact
gene
expression
interactions
RNA-binding
proteins,
particular
focus
roles
within
key
cellular
pathways.
Results
The
crucial
associated
resistance.
Notably,
changes
FILIP1L
TOM1L1,
related
these
SNPs,
mapped
using
pseudotime
trajectory
analysis,
which
traced
evolution
states.
TOM1L1
exhibited
dynamic
along
trajectory,
correlating
significant
shifts
cell
fate
decisions.
These
findings
underscore
potential
as
mediators
development
particularly
through
involvement
PI3K-Akt
Wnt
signaling
pathways,
critical
progression
drug
Conclusion
Our
emphasize
importance
influencing
cancer.
regulation
developmental
tumor
cells
sensitivity
provides
insights
into
complexity
results
pave
way
developing
targeted
therapies
that
modify
m6A-driven
offering
new
strategies
counteract
improve
patient
outcomes.
The Breast,
Год журнала:
2025,
Номер
unknown, С. 104483 - 104483
Опубликована: Апрель 1, 2025
Although
meta-analyses
have
demonstrated
survival
benefits
associated
with
primary
tumor
resection
in
MBC,
guidelines
lack
consensus
on
the
benefit
of
postoperative
radiation
therapy
(RT).
In
this
study,
we
included
1392
patients
de
novo
metastatic
breast
cancer
(dnMBC)
by
integrating
data
from
SEER
database
(2010-2019)
to
systematically
assess
efficacy
RT
and
develop
a
machine
learning-driven
prognostic
tool.
The
endpoint
was
overall
(OS).
Propensity
score
matching
(PSM)
results
showed
that
significantly
improved
OS
(HR
=
0.573,
95
%
CI
0.475-0.693),
but
gain
great
heterogeneity
among
different
subgroups.
It
is
found
HR-/HER2-or
HR+/HER2-subtypes
gained
significant
(p
<
0.001)
RT,
whereas
HER2+
subtype
did
not
any
since
effect
targeted
overshadowed
RT.
Further
risk
stratification
random
forest
(RSF)
model
revealed
high-risk
T4/N3
stage,
high
grade
poor
response
chemotherapy
had
prolonged
after
receiving
0.001),
while
low-risk
no
additional
benefit.
excellent
predictive
(training
set
C-index
0.741,
validation
0.720)
key
predictors
including
HER2
status,
grade.
research
team
developed
an
interactive
web
application
(https://lee2287171854.shinyapps.io/RSFshiny/)
based
model,
which
can
generate
individualized
scores
real-time
guide
clinical
decision-making.
This
study
first
propose
strategy
for
dnMBC,
innovatively
integrates
learning
tools
provide
new
paradigm
optimizing
precision
therapy.
Biomedicines,
Год журнала:
2024,
Номер
12(12), С. 2700 - 2700
Опубликована: Ноя. 26, 2024
Estrogen
receptor
α
(ERα)
drives
two
out
of
three
breast
cancers
and
therefore
ERα
is
a
major
therapeutic
target
for
ER-positive
cancer
patients.
Drugs
that
inhibit
activity
or
block
estrogen
synthesis
in
the
body
are
currently
being
used
clinic
to
treat
have
been
quite
successful
controlling
progression
majority
However,
often
becomes
resistant
these
endocrine
therapies,
leading
endocrine-resistant
metastatic
cancer,
very
aggressive
leads
death.
Recent
large-scale
genomic
studies
revealed
series
activating
somatic
mutations
gene
(ESR1)
Of
these,
Y537S
D538G
found
at
much
higher
rate
patients
with
cancer.
Remarkably,
produce
an
transcriptional
than
wild
type
absence
estradiol,
traditional
therapy
has
poor
efficacy
against
ER
mutants.
Therefore,
development
new
drugs
mutants
unmet
clinical
need
This
review
summarizes
recent
preclinical
trials
targeting
mutant
