Life,
Год журнала:
2023,
Номер
13(12), С. 2311 - 2311
Опубликована: Дек. 8, 2023
Breast
cancer
comprises
about
30%
of
all
new
female
cancers
each
year
and
is
the
most
common
malignant
in
women
United
States.
cell
lines
have
been
harnessed
for
many
years
as
a
foundation
vitro
analytic
studies
to
understand
use
prevention
therapy.
There
has
yet
be
compilation
works
analyze
pitfalls,
novel
discoveries,
essential
techniques
breast
line
scientific
context.
In
this
article,
we
review
history
their
origins,
well
molecular
pathways
that
pharmaceutical
drugs
apply
vivo.
Controversies
regarding
origins
certain
lines,
benefits
utilizing
Patient-Derived
Xenograft
(PDX)
versus
Cell-Derived
(CDX),
2D
3D
culturing
will
analyzed.
Novel
outcomes
from
epigenetic
discovery
with
dietary
compound
usage
are
also
discussed.
This
intended
create
foundational
tool
aid
investigators
when
choosing
multiple
expanding
areas
such
discovery,
xenograft
experimentation,
prevention,
among
other
areas.
Cancer Discovery,
Год журнала:
2020,
Номер
10(8), С. 1194 - 1209
Опубликована: Май 15, 2020
Abstract
EGFR
exon
20
insertion
driver
mutations
(Exon20ins)
in
non–small
cell
lung
cancer
(NSCLC)
are
insensitive
to
tyrosine
kinase
inhibitors
(TKI).
Amivantamab
(JNJ-61186372),
a
bispecific
antibody
targeting
EGFR–MET,
has
shown
preclinical
activity
TKI-sensitive
EGFR-mutated
NSCLC
models
and
an
ongoing
first-in-human
study
patients
with
advanced
NSCLC.
However,
the
of
amivantamab
Exon20ins-driven
tumors
not
yet
been
described.
Ba/F3
cells
patient-derived
cells/organoids/xenograft
harboring
diverse
Exon20ins
were
used
characterize
antitumor
mechanism
amivantamab.
inhibited
proliferation
by
effectively
downmodulating
EGFR–MET
levels
inducing
immune-directed
increased
IFNγ
secretion
various
models.
Importantly,
vivo
efficacy
was
superior
cetuximab
or
poziotinib,
experimental
Exon20ins-targeted
TKI.
produced
robust
tumor
responses
two
patients,
highlighting
important
translational
nature
this
work.
These
findings
provide
mechanistic
insight
into
support
its
continued
clinical
development
area
high
unmet
medical
need.
Significance:
Currently,
there
no
approved
targeted
therapies
for
Exon20ins–driven
Preclinical
data
here,
together
promising
phase
I
study,
strongly
further
investigation
This
article
is
highlighted
In
Issue
feature,
p.
1079
Journal of Translational Medicine,
Год журнала:
2022,
Номер
20(1)
Опубликована: Май 10, 2022
Abstract
The
establishing
of
the
first
cancer
models
created
a
new
perspective
on
identification
and
evaluation
anti-cancer
therapies
in
preclinical
studies.
Patient-derived
xenograft
are
by
tumor
tissue
engraftment.
These
accurately
represent
biology
heterogeneity
different
cancers
recapitulate
microenvironment.
features
have
made
it
reliable
model
along
with
development
humanized
models.
Therefore,
they
used
many
studies,
such
as
drugs,
co-clinical
trials,
personalized
medicine,
immunotherapy,
PDX
biobanks.
This
review
summarizes
patient-derived
procedures,
drug
applications
various
cancers,
challenges
limitations.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Апрель 12, 2023
Abstract
Patient-derived
xenograft
(PDX)
models,
in
which
tumor
tissues
from
patients
are
implanted
into
immunocompromised
or
humanized
mice,
have
shown
superiority
recapitulating
the
characteristics
of
cancer,
such
as
spatial
structure
cancer
and
intratumor
heterogeneity
cancer.
Moreover,
PDX
models
retain
genomic
features
across
different
stages,
subtypes,
diversified
treatment
backgrounds.
Optimized
engraftment
procedures
modern
technologies
multi-omics
deep
learning
enabled
a
more
comprehensive
depiction
molecular
landscape
boosted
utilization
models.
These
irreplaceable
advantages
make
an
ideal
choice
studies,
preclinical
trials
novel
drugs,
validating
drug
combinations,
screening
drug-sensitive
patients,
exploring
resistance
mechanisms.
In
this
review,
we
gave
overview
history
process
model
establishment.
Subsequently,
review
presents
strengths
weaknesses
highlights
integration
research.
Finally,
delineated
broad
application
chemotherapy,
targeted
therapy,
immunotherapy,
other
therapies.
Cancers,
Год журнала:
2022,
Номер
14(4), С. 976 - 976
Опубликована: Фев. 15, 2022
Emerging
evidence
suggests
that
a
small
subpopulation
of
cancer
stem
cells
(CSCs)
is
responsible
for
initiation,
progression,
and
metastasis
cascade
in
tumors.
CSCs
share
characteristics
with
normal
cells,
i.e.,
self-renewal
differentiation
potential,
suggesting
they
can
drive
progression.
Consequently,
targeting
to
prevent
tumor
growth
or
regrowth
might
offer
chance
lead
the
fight
against
cancer.
create
their
niche,
specific
area
within
tissue
unique
microenvironment
sustains
vital
functions.
Interactions
between
niches
play
critical
role
regulating
CSCs'
tumorigenesis.
Differences
observed
frequency
CSCs,
due
phenotypic
plasticity
many
remain
challenge
therapeutics,
since
modulate
transcriptional
activities
into
more
stem-like
state
protect
themselves
from
destruction.
This
represents
an
essential
step
future
therapeutic
approaches.
Regarding
self-renewal,
are
modulated
by
same
molecular
pathways
found
such
as
Wnt/β-catenin
signaling,
Notch
Hedgehog
signaling.
Another
key
characteristic
resistance
standard
chemotherapy
radiotherapy
treatments,
capacity
rest
quiescent
state.
review
will
analyze
primary
mechanisms
involved
CSC
tumorigenesis,
particular
attention
roles
progression
benign
malignant
diseases;
examine
perspectives
on
identification
new
markers
better
control
well
dissecting
process.
Frontiers in Oncology,
Год журнала:
2023,
Номер
13
Опубликована: Апрель 28, 2023
Heterogeneity
describes
the
differences
among
cancer
cells
within
and
between
tumors.
It
refers
to
describing
variations
in
morphology,
transcriptional
profiles,
metabolism,
metastatic
potential.
More
recently,
field
has
included
characterization
of
tumor
immune
microenvironment
depiction
dynamics
underlying
cellular
interactions
promoting
ecosystem
evolution.
been
found
most
tumors
representing
one
challenging
behaviors
ecosystems.
As
critical
factors
impairing
long-term
efficacy
solid
therapy,
heterogeneity
leads
resistance,
more
aggressive
metastasizing,
recurrence.
We
review
role
main
models
emerging
single-cell
spatial
genomic
technologies
our
understanding
heterogeneity,
its
contribution
lethal
outcomes,
physiological
challenges
consider
designing
therapies.
highlight
how
dynamically
evolve
because
leverage
this
unleash
recognition
through
immunotherapy.
A
multidisciplinary
approach
grounded
novel
bioinformatic
computational
tools
will
allow
reaching
integrated,
multilayered
knowledge
required
implement
personalized,
efficient
therapies
urgently
for
patients.
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
Cell,
Год журнала:
2020,
Номер
181(7), С. 1596 - 1611.e27
Опубликована: Июнь 1, 2020
Oncogenic
transformation
is
associated
with
profound
changes
in
cellular
metabolism,
but
whether
tracking
these
can
improve
disease
stratification
or
influence
therapy
decision-making
largely
unknown.
Using
the
iKnife
to
sample
aerosol
of
cauterized
specimens,
we
demonstrate
a
new
mode
real-time
diagnosis,
coupling
metabolic
phenotype
mutant
PIK3CA
genotype.
results
an
increase
arachidonic
acid
and
concomitant
overproduction
eicosanoids,
acting
promote
cell
proliferation
beyond
cell-autonomous
manner.
Mechanistically,
drives
multimodal
signaling
network
involving
mTORC2-PKCζ-mediated
activation
calcium-dependent
phospholipase
A2
(cPLA2).
Notably,
inhibiting
cPLA2
synergizes
fatty
acid-free
diet
restore
immunogenicity
selectively
reduce
PIK3CA-induced
tumorigenicity.
Besides
highlighting
potential
for
phenotyping
stratified
medicine,
this
study
reveals
important
role
activated
PI3K
regulating
uncovering
targetable
vulnerability
that
depends
on
dietary
fat
restriction.
VIDEO
ABSTRACT.
International Journal of Molecular Sciences,
Год журнала:
2020,
Номер
21(11), С. 4118 - 4118
Опубликована: Июнь 9, 2020
Recent
advances
in
the
development
of
new
methods
cancer
immunotherapy
require
production
complex
animal
models
that
reliably
reflect
complexity
tumor
and
its
microenvironment.
Mice
are
good
animals
to
create
because
they
low
cost,
have
a
short
reproductive
cycle,
exhibit
high
growth
rates,
can
be
easily
genetically
modified.
However,
obvious
problem
these
is
failure
rate
observed
human
clinical
trials
after
promising
results
obtained
mouse
models.
In
order
increase
reliability
mice,
model
should
heterogeneity
tumor,
contain
components
microenvironment,
particular
immune
cells,
which
action
immunotherapeutic
drugs
directed.
This
review
discusses
current
immunocompetent
immunocompromised
tumors
used
evaluate
effectiveness
agents,
chimeric
antigen
receptor
(CAR)
T-cells
checkpoint
inhibitors.
