Biomolecules and Biomedicine,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 20, 2024
Breast
cancer
(BC)
is
a
prevalent
malignant
tumor
that
poses
significant
health
risk
to
women.
The
complexity
of
basic
BC
research
and
clinical
treatment
influenced
by
multiple
factors,
including
age,
fertility,
hormone
metabolism,
molecular
subtypes,
grading
staging.
Traditional
in
vitro
models
often
fall
short
meeting
modern
demands,
whereas
organoids—an
emerging
3D
primary
culture
technology—offer
unique
platform
better
replicates
the
microenvironment
(TME).
Coupled
with
advances
high-throughput
sequencing
technologies,
organoids
have
become
increasingly
valuable
biological
chemical
research.
Currently,
most
widely
used
organoid
model
patient-derived
(PDO)
model,
which
generated
directly
from
original
tissues.
This
paper
aims
summarize
current
status
PDO
across
various
highlighting
recent
genetics,
mechanisms
drug
resistance,
identification
new
therapeutic
targets,
approaches
personalized
treatment.
In
conclusion,
development
precision
medicine
urgently
requires
capable
accurately
simulating
subtypes
patients.
review
will
examine
challenges
future
prospects
research,
offering
insights
into
fundamental
paving
way
for
more
effective
therapies.
MedComm,
Journal Year:
2025,
Volume and Issue:
6(2)
Published: Jan. 19, 2025
Abstract
The
patient‐derived
xenograft
(PDX)
model
is
a
crucial
in
vivo
extensively
employed
cancer
research
that
has
been
shown
to
maintain
the
genomic
characteristics
and
pathological
structure
of
patients
across
various
subtypes,
metastatic,
diverse
treatment
histories.
Various
strategies
utilized
PDX
models
can
offer
valuable
insights
into
mechanisms
tumor
progression,
drug
resistance,
development
novel
therapies.
This
review
provides
comprehensive
overview
establishment
applications
models.
We
present
an
history
current
status
models,
elucidate
construction
methodologies
for
different
tumors,
conduct
comparative
analysis
highlight
distinct
advantages
limitations
this
relation
other
are
elucidated
domain
comprehending
underlying
therapy,
which
highlights
broad
fields
chemotherapy,
targeted
delivery
systems,
combination
antibody–drug
conjugates
radiotherapy.
Furthermore,
with
multiomics
single‐cell
analyses
also
emphasized.
application
clinical
personalized
medicine
additionally
Cancer Cell,
Journal Year:
2025,
Volume and Issue:
43(3), P. 464 - 481.e14
Published: March 1, 2025
Highlights•Atirmociclib
(PF-07220060)
is
a
next-generation
CDK4
selective
inhibitor•Impact
reduction
on
neutrophils
was
in
proportion
to
increase
selectivity•Greater
target
coverage
results
deeper
anti-tumor
responses•Combinatorial
agents
further
atirmociclib
efficacySummaryCDK4/6
inhibitors
have
revolutionized
treatment
of
hormone
receptor
positive
(HR+),
HER2
non-amplified
(HER2−)
breast
cancer.
Yet,
all
"dual"
CDK4/6
show
common
dose-limiting
hematologic
toxicities,
foremost
neutropenia.
This
poses
challenges
provide
these
at
concentrations
necessary
extinguish
cell
cycling
tumors.
HR+
cancer
cells
are
highly
dependent
but
not
CDK6.
By
contrast,
dispensable
for
human
bone
marrow
derived
cells,
due
the
primary
and
compensatory
role
CDK6
hematopoiesis.
prompted
us
develop
(PF-07220060),
inhibitor.
Atirmociclib's
impact
circulating
reduced,
with
its
versus
selectivity.
Realized
dose
intensification
led
greater
inhibition
responses,
pointing
as
limiting
factor
inhibitor
efficacy.
We
also
highlight
combinatorial
that
may
counter
acquired
resistance
widen
clinical
application.Graphical
abstract
ESMO Open,
Journal Year:
2024,
Volume and Issue:
9(3), P. 102247 - 102247
Published: Feb. 23, 2024
Tumor
heterogeneity
represents
a
major
challenge
in
breast
cancer,
being
associated
with
disease
progression
and
treatment
resistance.
Precision
medicine
has
been
extensively
applied
to
dissect
tumor
and,
through
deeper
molecular
understanding
of
the
disease,
personalize
therapeutic
strategies.
In
last
years,
technological
advances
have
widely
improved
cancer
biology
several
trials
developed
translate
these
new
insights
into
clinical
practice,
ultimate
aim
improving
patients'
outcomes.
era
oncology,
genomics
analyses
other
methodologies
are
shaping
algorithm
care.
this
manuscript,
we
review
main
steps
precision
predict
drug
sensitivity
from
translational
point
view.
Genomic
developments
their
implications
discussed,
along
advancements
that
could
broaden
applications.
Current
achievements
put
perspective
provide
an
overview
state-of-art
oncology
as
well
identify
future
research
directions.
Cancer Drug Resistance,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 22, 2025
This
review
offers
an
expert
perspective
on
biomarkers,
CDK4/6
inhibitor
efficacy,
and
therapeutic
approaches
for
managing
hormone
receptor-positive
(HR+),
human
epidermal
growth
factor
receptor-negative
(HER2-)
advanced
breast
cancer
(ABC),
particularly
after
progression.
Key
trials
have
demonstrated
that
combining
inhibitors
with
endocrine
therapy
(ET)
significantly
improves
progression-free
survival
(PFS),
median
durations
ranging
from
14.8
to
26.7
months,
overall
(OS),
reaching
up
53.7
months.
Actionable
such
as
PIK3CA
ESR1
mutations,
emerged
pivotal
tools
guide
second-line
treatment
decisions,
enabling
the
use
of
targeted
therapies
like
alpelisib
elacestrant
emphasizing
important
role
biomarkers
in
guiding
selection
therapy.
overview
aims
provide
clinicians
a
practical
up-to-date
framework
inform
decisions
improve
patient
care
context
this
challenging
disease.
Additionally,
we
emerging
novel
strategies
address
difficult
clinical
landscape.
The
combination
of
CDK4/6
inhibitors
(CDK4/6i)
and
endocrine
therapy
has
revolutionized
treatment
for
hormone
receptor-positive
(HR+)
metastatic
breast
cancer.
However,
the
emergence
resistance
in
most
patients
often
leads
to
discontinuation
with
no
consensus
on
effective
second-line
therapies.
therapeutic
benefits
maintaining
CDK4/6i
or
incorporating
CDK2
(CDK2i)
after
disease
progression
remain
unclear.
Here,
we
demonstrate
that
sustained
therapy,
either
alone
combined
CDK2i,
significantly
suppresses
growth
drug-resistant
HR
+
Continued
induces
a
non-canonical
pathway
retinoblastoma
protein
(Rb)
inactivation
via
post-translational
degradation,
resulting
diminished
E2F
activity
delayed
G1
progression.
Importantly,
our
data
highlight
CDK2i
should
be
effectively
suppress
overcome
resistance.
We
also
identify
cyclin
E
overexpression
as
key
driver
inhibition.
These
findings
provide
crucial
insights
into
overcoming
cancer,
supporting
continued
use
strategic
incorporation
improve
outcomes.
MedComm,
Journal Year:
2024,
Volume and Issue:
5(10)
Published: Sept. 25, 2024
Patient-derived
xenografts
(PDX)
involve
transplanting
patient
cells
or
tissues
into
immunodeficient
mice,
offering
superior
disease
models
compared
with
cell
line
and
genetically
engineered
mice.
In
contrast
to
traditional
cell-line
PDX
harbor
the
molecular
biologic
features
from
original
tumor
are
generationally
stable.
This
high
fidelity
makes
particularly
suitable
for
preclinical
coclinical
drug
testing,
therefore
better
predicting
therapeutic
efficacy.
Although
becoming
more
useful,
several
factors
influencing
their
reliability
predictive
power
not
well
understood.
Several
existing
studies
have
looked
possibility
that
could
be
important
in
enhancing
our
knowledge
regard
genetics,
biomarker
discovery,
personalized
medicine;
however,
a
number
of
problems
still
need
addressed,
such
as
cost
time-consuming
processes
involved,
together
variability
take
rates.
review
addresses
these
gaps
by
detailing
methodologies
generate
models,
application
cancer
research,
advantages
over
other
models.
Further,
it
elaborates
on
how
artificial
intelligence
machine
learning
were
incorporated
fast-track
evaluation.
is
an
overview
progress
has
been
done
so
far
using
research
shows
potential
further
improved
improving
understanding
oncogenesis.
Cancer Medicine,
Journal Year:
2024,
Volume and Issue:
13(10)
Published: May 1, 2024
Abstract
Background
Cyclin‐dependent
kinase
(CDK)
4/6
inhibitor
plus
endocrine
therapy
(ET)
become
standard‐of‐care
for
patients
with
hormone
receptor‐positive,
human
epidermal
growth
factor
receptor‐2
negative
(HR+/HER2−)
metastatic
breast
cancer
(MBC).
However,
the
optimal
therapeutic
paradigm
after
progression
on
CDK4/6
remains
unclear.
This
study
aimed
to
evaluate
efficacy
and
safety
of
abemaciclib
switching
ET
versus
chemotherapy
prior
palbociclib‐based
in
Chinese
HR+/HER2−
MBC.
Methods
From
414
consecutive
MBC
who
had
been
treated
palbociclib
from
September
2018
May
2022
Peking
University
Cancer
Hospital,
we
identified
80
received
or
palbociclib,
matched
age,
original
stage
at
diagnosis,
disease‐free
interval,
tumor
burden
1:1
ratio.
The
primary
endpoint
was
progression‐free
survival
(PFS)
compared
using
Kaplan–Meier
method.
A
Cox
proportional
hazard
model
performed
identify
clinical
factors
associated
PFS
group.
Results
median
6.0
months
(95%
confidence
interval
[CI]:
3.94–8.06)
group
4.0
CI,
2.52–5.49)
(
p
=
0.667).
And,
there
no
difference
between
sequential
nonsequential
arm
(6.0
vs.
months)
though
fewer
lines
systemic
longer
arm.
as
first‐line
a
significantly
≥2nd‐line
(11.0
5.0
months,
0.043).
Based
multivariable
analysis,
ER+/PR+
an
independent
PFS.
There
significant
overall
groups
0.069).
Conclusion
Our
findings
indicate
that
might
be
one
feasible
treatment
options
addition
chemotherapy.
