Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Март 25, 2025
The
persistently
high
mortality
rates
associated
with
cancer
underscore
the
imperative
need
for
innovative,
efficacious,
and
safer
therapeutic
agents,
as
well
a
more
nuanced
understanding
of
tumor
biology.
Patient-derived
organoids
(PDOs)
have
emerged
innovative
preclinical
models
significant
translational
potential,
capable
accurately
recapitulating
structural,
functional,
heterogeneous
characteristics
primary
tumors.
When
integrated
cutting-edge
genomic
tools
such
CRISPR,
PDOs
provide
powerful
platform
identifying
driver
genes
novel
targets.
This
comprehensive
review
delves
into
recent
advancements
in
CRISPR-mediated
functional
screens
leveraging
across
diverse
types,
highlighting
their
pivotal
role
high-throughput
genomics
microenvironment
(TME)
modeling.
Furthermore,
this
highlights
synergistic
potential
integrating
CRISPR
immunotherapy,
focusing
on
uncovering
immune
evasion
mechanisms
improving
efficacy
immunotherapeutic
approaches.
Together,
these
technologies
offer
promise
advancing
precision
oncology.
Язык: Английский
High-Throughput Screening to Identify Novel Compounds Affecting the Genome Editing Efficiency of CRISPR System
Molecules,
Год журнала:
2025,
Номер
30(8), С. 1811 - 1811
Опубликована: Апрель 17, 2025
Genome
editing
is
a
promising
therapeutic
strategy
for
genetic
disorders
by
modifying
the
genome
precisely,
especially
CRISPR/Cas9
system.
However,
major
limitation
of
in
gene
therapy
biosafety
issues
caused
off-target
effects.
Compounds
that
can
modulate
efficiency
system,
those
reducing
effects,
are
potentially
useful
pharmacological
tools
improving
effectiveness
and
safety
editing.
Here,
we
performed
high-throughput
screening
HEK
293FT
cells
to
discover
compounds
decrease
or
increase
system
from
9930
compounds.
After
two
rounds
screening,
identified
CP-724714,
ErbB2
(HER2)
tyrosine
kinase
inhibitor,
decreased
reduced
effects
suppressing
CRISPR/Cas9,
was
thus
named
CRISPR
decelerator
(or
inhibitor),
while
Clofarabine,
DNA
synthesis
increased
accelerator.
We
further
four
(Tranilast,
Cerulenin,
Rosolic
acid
Resveratrol)
affected
single-strand
annealing
(SSA)
repair.
Among
them,
Tranilast,
Cerulenin
potential
SSA
decelerators,
Resveratrol
These
may
be
optimizing
mammalian
manipulation
techniques.
Язык: Английский