Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: June 6, 2022
Abstract
Patient-derived
organoids
resemble
the
biology
of
tissues
and
tumors,
enabling
ex
vivo
modeling
human
diseases.
They
have
heterogeneous
morphologies
with
unclear
biological
causes
relationship
to
treatment
response.
Here,
we
use
high-throughput,
image-based
profiling
quantify
phenotypes
over
5
million
individual
colorectal
cancer
after
>500
small
molecules.
Integration
data
using
multi-omics
identifies
axes
morphological
variation
across
organoids:
Organoid
size
is
linked
IGF1
receptor
signaling,
cystic
vs.
solid
organoid
architecture
associated
LGR5
+
stemness.
Treatment-induced
morphology
reflects
viability,
drug
mechanism
action,
biologically
interpretable.
Inhibition
MEK
leads
reorganization
increases
expression
,
while
inhibition
mTOR
induces
signaling.
In
conclusion,
identify
shared
for
morphology,
their
underlying
mechanisms,
pharmacological
interventions
ability
move
along
them.
Cancer Cell,
Journal Year:
2021,
Volume and Issue:
40(1), P. 26 - 35
Published: Dec. 23, 2021
Functional
precision
medicine
is
a
strategy
whereby
live
tumor
cells
from
affected
individuals
are
directly
perturbed
with
drugs
to
provide
immediately
translatable,
personalized
information
guide
therapy.
The
heterogeneity
of
human
cancer
has
led
the
realization
that
approaches
needed
improve
treatment
outcomes.
Precision
oncology
traditionally
used
static
features
dictate
which
therapies
should
be
used.
Static
can
include
expression
key
targets
or
genomic
analysis
mutations
identify
therapeutically
targetable
"drivers."
Although
surprisingly
small
proportion
derive
clinical
benefit
approach,
functional
additional
regarding
vulnerabilities.
We
discuss
emerging
technologies
for
as
well
limitations
and
challenges
in
using
these
assays
trials
will
necessary
determine
whether
outcomes
eventually
become
standard
tool
oncology.
Cancer Cell,
Journal Year:
2024,
Volume and Issue:
42(2), P. 180 - 197
Published: Feb. 1, 2024
The
past
decade
has
witnessed
significant
advances
in
the
systemic
treatment
of
advanced
hepatocellular
carcinoma
(HCC).
Nevertheless,
newly
developed
strategies
have
not
achieved
universal
success
and
HCC
patients
frequently
exhibit
therapeutic
resistance
to
these
therapies.
Precision
represents
a
paradigm
shift
cancer
recent
years.
This
approach
utilizes
unique
molecular
characteristics
individual
patient
personalize
modalities,
aiming
maximize
efficacy
while
minimizing
side
effects.
Although
precision
shown
multiple
types,
its
application
remains
infancy.
In
this
review,
we
discuss
key
aspects
HCC,
including
biomarkers,
classifications,
heterogeneity
tumor
microenvironment.
We
also
propose
future
directions,
ranging
from
revolutionizing
current
methodologies
personalizing
therapy
through
functional
assays,
which
will
accelerate
next
phase
advancements
area.
Cell,
Journal Year:
2022,
Volume and Issue:
185(15), P. 2756 - 2769
Published: July 1, 2022
For
decades,
insight
into
fundamental
principles
of
human
biology
and
disease
has
been
obtained
primarily
by
experiments
in
animal
models.
While
this
allowed
researchers
to
understand
many
biological
processes
great
detail,
some
developmental
mechanisms
have
proven
difficult
study
due
inherent
species
differences.
The
advent
organoid
technology
more
than
10
years
ago
established
laboratory-grown
organ
tissues
as
an
additional
model
system
recapitulate
human-specific
aspects
biology.
use
3D
organoids,
well
other
advances
single-cell
technologies,
revealed
unprecedented
insights
mechanisms,
especially
those
that
distinguish
humans
from
species.
This
review
highlights
novel
with
a
focus
on
how
generated
better
understanding
development
disease.
Cancer Discovery,
Journal Year:
2022,
Volume and Issue:
13(2), P. 364 - 385
Published: Nov. 9, 2022
Abstract
A
lack
of
models
that
recapitulate
the
complexity
human
bone
marrow
has
hampered
mechanistic
studies
normal
and
malignant
hematopoiesis
validation
novel
therapies.
Here,
we
describe
a
step-wise,
directed-differentiation
protocol
in
which
organoids
are
generated
from
induced
pluripotent
stem
cells
committed
to
mesenchymal,
endothelial,
hematopoietic
lineages.
These
3D
structures
capture
key
features
marrow—stroma,
lumen-forming
sinusoids,
myeloid
including
proplatelet-forming
megakaryocytes.
The
supported
engraftment
survival
patients
with
blood
malignancies,
cancer
types
notoriously
difficult
maintain
ex
vivo.
Fibrosis
organoid
occurred
following
TGFβ
stimulation
myelofibrosis
but
not
healthy
donor–derived
cells,
validating
this
platform
as
powerful
tool
for
their
interactions
within
marrow–like
milieu.
This
enabling
technology
is
likely
accelerate
discovery
prioritization
targets
disorders
cancers.
Significance:
We
present
supports
growth
primary
lymphoid
model
allows
cancers
context
microenvironment
provides
much-needed
vivo
new
therapeutics.
See
related
commentary
by
Derecka
Crispino,
p.
263.
article
highlighted
In
Issue
feature,
247
Science Translational Medicine,
Journal Year:
2023,
Volume and Issue:
15(706)
Published: July 26, 2023
Organoid
models
have
the
potential
to
recapitulate
biological
and
pharmacotypic
features
of
parental
tumors.
Nevertheless,
integrative
pharmaco-proteogenomics
analysis
for
drug
response
biomarker
investigation
precision
therapy
patients
with
liver
cancer
are
still
lacking.
We
established
a
patient-derived
organoid
biobank
(LICOB)
that
comprehensively
represents
histological
molecular
characteristics
various
types
as
determined
by
multiomics
profiling,
including
genomic,
epigenomic,
transcriptomic,
proteomic
analysis.
Proteogenomic
profiling
LICOB
identified
proliferative
metabolic
subtypes
linked
patient
prognosis.
High-throughput
screening
revealed
distinct
patterns
each
subtype
were
associated
specific
signatures.
Through
analyses
data,
we
responses
predicted
combinations
personalized
treatment.
The
synergistic
inhibition
effect
mTOR
inhibitor
temsirolimus
multitargeted
tyrosine
kinase
lenvatinib
was
validated
in
organoids
xenografts
models.
also
provide
user-friendly
web
portal
help
serve
biomedical
research
community.
Our
study
is
rich
resource
biology
pharmacological
dependencies
may
enable
functional
medicine.
