Pharmacology & Therapeutics,
Год журнала:
2024,
Номер
257, С. 108631 - 108631
Опубликована: Март 11, 2024
Mouse
models
of
disease
play
a
pivotal
role
at
all
stages
cancer
drug
development.
Cell-line
derived
subcutaneous
tumour
are
predominant
in
early
discovery,
but
there
is
growing
recognition
the
importance
more
complex
orthotopic
and
metastatic
for
understanding
both
target
biology
correct
tissue
context,
impact
microenvironment
immune
system
responses
to
treatment.
The
aim
this
review
highlight
value
that
bring
study
development
while
pointing
out
those
most
likely
be
encountered
literature.
Important
developments
models,
such
as
increasing
use
passage
patient
material
(PDXs,
organoids)
humanised
mouse
discussed,
these
approaches
have
potential
increase
predictive
preclinical
studies,
ultimately
improve
success
rate
anticancer
drugs
clinical
trials.
Molecular Omics,
Год журнала:
2020,
Номер
17(1), С. 29 - 42
Опубликована: Окт. 9, 2020
Data-independent
acquisition
mass
spectrometry
(DIA-MS)
is
a
next
generation
proteomic
methodology
that
generates
permanent
digital
proteome
maps
offering
highly
reproducible
retrospective
analysis
of
cellular
and
tissue
specimens.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Фев. 18, 2021
Abstract
Therapy
resistance
and
metastatic
processes
in
prostate
cancer
(PCa)
remain
undefined,
due
to
lack
of
experimental
models
that
mimic
different
disease
stages.
We
describe
an
androgen-dependent
PCa
patient-derived
xenograft
(PDX)
model
from
treatment-naïve,
soft
tissue
metastasis
(PNPCa).
RNA
whole-exome
sequencing
the
PDX
organoids
confirmed
transcriptomic
genomic
similarity
primary
tumor.
PNPCa
harbors
BRCA2
CHD1
somatic
mutations,
shows
SPOP/FOXA1
-like
signature
microsatellite
instability,
which
occurs
3%
advanced
has
never
been
modeled
vivo.
Comparison
treatment-naïve
with
additional
PDXs
(BM18,
LAPC9),
a
medium-throughput
organoid
screen
FDA-approved
compounds,
revealed
differential
drug
sensitivities.
Multikinase
inhibitors
(ponatinib,
sunitinib,
sorafenib)
were
broadly
effective
on
all
PDX-
cases
acquired
standard-of-care
compounds.
This
proof-of-principle
study
may
provide
preclinical
tool
responses
newly
identified,
repurposed
Organoids
are
three-dimensional
(3D)
miniaturized
versions
of
organs
or
tissues
that
derived
from
cells
with
stem
potential
and
can
self-organize
differentiate
into
3D
cell
masses,
recapitulating
the
morphology
functions
their
in
vivo
counterparts.
Organoid
culture
is
an
emerging
technology,
organoids
various
tissues,
such
as
brain,
lung,
heart,
liver,
kidney,
have
been
generated.
Compared
traditional
bidimensional
culture,
organoid
systems
unique
advantage
conserving
parental
gene
expression
mutation
characteristics,
well
long-term
maintenance
function
biological
characteristics
vitro.
All
these
features
open
up
new
opportunities
for
drug
discovery,
large-scale
screening,
precision
medicine.
Another
major
application
disease
modeling,
especially
hereditary
diseases
difficult
to
model
vitro
modeled
by
combining
genome
editing
technologies.
Herein,
we
introduce
development
current
advances
technology
field.
We
focus
on
applications
basic
biology
clinical
research,
also
highlight
limitations
future
perspectives.
hope
this
review
provide
a
valuable
reference
developments
organoids.
Clinical and Translational Medicine,
Год журнала:
2021,
Номер
11(2)
Опубликована: Фев. 1, 2021
Abstract
Carcinomas
are
complex
heterocellular
systems
containing
epithelial
cancer
cells,
stromal
fibroblasts,
and
multiple
immune
cell‐types.
Cell‐cell
communication
between
these
tumor
microenvironments
(TME)
cells
drives
progression
influences
response
to
existing
therapies.
In
order
provide
better
treatments
for
patients,
we
must
understand
how
various
cell‐types
collaborate
within
the
TME
drive
consider
signals
present
different
types.
To
investigate
tissues
function,
need
a
model
measure
both
transferred
that
information
is
processed
cells.
The
interplay
of
collaboration
requires
cell‐cell
communication.
This
article
aims
review
current
in
vitro
vivo
mono‐cellular
multi‐cellular
cultures
models
colorectal
(CRC),
explore
they
can
be
used
single‐cell
multi‐omics
approaches
isolating
types
molecules
from
required
distinguish
normal
Integrating
signaling
measurements
models,
through
understanding
cell
identity
communicate,
will
help
predict
drug
sensitivities
between‐
within‐patients
responses.
Pharmacological Reviews,
Год журнала:
2022,
Номер
74(3), С. 799 - 824
Опубликована: Июнь 23, 2022
Adenosine
is
an
evolutionary
ancient
metabolic
regulator
linking
energy
state
to
physiologic
processes,
including
immunomodulation
and
cell
proliferation.
Tumors
create
adenosine-rich
immunosuppressive
microenvironment
through
the
increased
release
of
ATP
from
dying
stressed
cells
its
ectoenzymatic
conversion
into
adenosine.
Therefore,
adenosine
pathway
becomes
important
therapeutic
target
improve
effectiveness
immune
therapies.
Prior
research
has
focused
largely
on
two
major
ectonucleotidases,
ectonucleoside
triphosphate
diphosphohydrolase
1/cluster
differentiation
(CD)39
ecto-5′-nucleotidase/CD73,
which
catalyze
breakdown
extracellular
adenosine,
subsequent
activation
different
subtypes
receptors
with
mixed
findings
antitumor
protumor
effects.
New
findings,
needed
for
more
effective
approaches,
require
consideration
redundant
pathways
controlling
intratumoral
levels,
alternative
NAD-inactivating
CD38-ectonucleotide
pyrophosphatase
phosphodiesterase
(ENPP)1-CD73
axis,
counteracting
ATP-regenerating
pathway,
cellular
uptake
phosphorylation
by
kinase.
This
review
provides
a
holistic
view
intracellular
metabolism
as
integrated
complex
network
summarizes
recent
data
underlying
mechanisms
precursors
ADP
control
cancer
immunosurveillance,
tumor
angiogenesis,
lymphangiogenesis,
cancer-associated
thrombosis,
blood
flow,
perfusion.
Special
attention
given
differences
commonalities
in
purinome
cancers,
heterogeneity
microenvironment,
subcellular
compartmentalization
system,
novel
roles
purine-converting
enzymes
targets
therapy.
Significance
Statement
The
discovery
role
checkpoint
led
development
strategies
targeting
signaling
multiple
clinical
trials
preclinical
models.
Here
we
identify
gaps
knowledge
that
need
be
filled
gain
agents
key
components
and,
this
basis,
provide
network.
The
advent
of
iPSCs
has
brought
about
a
significant
transformation
in
stem
cell
research,
opening
up
promising
avenues
for
advancing
cancer
treatment.
formation
is
multifaceted
process
influenced
by
genetic,
epigenetic,
and
environmental
factors.
offer
distinctive
platform
investigating
the
origin
cancer,
paving
way
novel
approaches
to
treatment,
drug
testing,
tailored
medical
interventions.
This
review
article
will
provide
an
overview
science
behind
iPSCs,
current
limitations
challenges
iPSC-based
therapy,
ethical
social
implications,
comparative
analysis
with
other
types
also
discuss
applications
tumorigenesis,
future
tumorigenesis
highlight
successful
case
studies
utilizing
research.
conclusion
summarize
advancements
made
research
importance
continued
investment
iPSC
unlock
full
potential
these
cells.
