Oncogene,
Journal Year:
2023,
Volume and Issue:
42(47), P. 3457 - 3490
Published: Oct. 20, 2023
Abstract
Evidence
from
physical
sciences
in
oncology
increasingly
suggests
that
the
interplay
between
biophysical
tumor
microenvironment
and
genetic
regulation
has
significant
impact
on
progression.
Especially,
cells
associated
stromal
not
only
alter
their
own
cytoskeleton
properties
but
also
remodel
with
anomalous
properties.
Together,
these
altered
mechano-omics
of
tissues
constituents
fundamentally
shift
mechanotransduction
paradigms
tumorous
activate
oncogenic
signaling
within
neoplastic
niche
to
facilitate
However,
current
findings
biophysics
are
limited,
scattered,
often
contradictory
multiple
contexts.
Systematic
understanding
how
cues
influence
pathophysiology
is
still
lacking.
This
review
discusses
recent
different
schools
have
arisen
multi-scale
mechanobiology
cutting-edge
technologies.
These
range
molecular
cellular
whole
tissue
level
feature
functional
crosstalk
signaling.
We
highlight
potential
alterations
as
new
therapeutic
targets
for
cancer
mechanomedicine.
framework
reconciles
opposing
opinions
field,
proposes
directions
future
research,
conceptualizes
novel
mechanomedicine
landscape
overcome
inherent
shortcomings
conventional
diagnosis
therapies.
Cancer Discovery,
Journal Year:
2021,
Volume and Issue:
11(4), P. 933 - 959
Published: April 1, 2021
Abstract
Strategies
to
therapeutically
target
the
tumor
microenvironment
(TME)
have
emerged
as
a
promising
approach
for
cancer
treatment
in
recent
years
due
critical
roles
of
TME
regulating
progression
and
modulating
response
standard-of-care
therapies.
Here,
we
summarize
current
knowledge
regarding
most
advanced
TME-directed
therapies,
which
either
been
clinically
approved
or
are
currently
being
evaluated
trials,
including
immunotherapies,
antiangiogenic
drugs,
treatments
directed
against
cancer-associated
fibroblasts
extracellular
matrix.
We
also
discuss
some
challenges
associated
with
future
perspectives
this
evolving
field.
Significance:
This
review
provides
comprehensive
analysis
therapies
targeting
TME,
combining
discussion
underlying
basic
biology
clinical
evaluation
different
therapeutic
approaches,
highlighting
perspectives.
Nature,
Journal Year:
2022,
Volume and Issue:
611(7935), P. 365 - 373
Published: Nov. 2, 2022
Abstract
Cells
respond
to
physical
stimuli,
such
as
stiffness
1
,
fluid
shear
stress
2
and
hydraulic
pressure
3,4
.
Extracellular
viscosity
is
a
key
cue
that
varies
under
physiological
pathological
conditions,
cancer
5
However,
its
influence
on
biology
the
mechanism
by
which
cells
sense
changes
in
are
unknown.
Here
we
demonstrate
elevated
counterintuitively
increases
motility
of
various
cell
types
two-dimensional
surfaces
confinement,
dissemination
from
three-dimensional
tumour
spheroids.
Increased
mechanical
loading
imposed
induces
an
actin-related
protein
2/3
(ARP2/3)-complex-dependent
dense
actin
network,
enhances
Na
+
/H
exchanger
(NHE1)
polarization
through
actin-binding
partner
ezrin.
NHE1
promotes
swelling
increased
membrane
tension,
which,
turn,
activates
transient
receptor
potential
cation
vanilloid
4
(TRPV4)
mediates
calcium
influx,
leading
RHOA-dependent
contractility.
The
coordinated
action
remodelling/dynamics,
NHE1-mediated
RHOA-based
contractility
facilitates
enhanced
at
viscosities.
Breast
pre-exposed
acquire
TRPV4-dependent
memory
transcriptional
control
Hippo
pathway,
migration
zebrafish,
extravasation
chick
embryos
lung
colonization
mice.
Cumulatively,
extracellular
regulates
both
short-
long-term
cellular
processes
with
pathophysiological
relevance
biology.
Frontiers in Cell and Developmental Biology,
Journal Year:
2021,
Volume and Issue:
9
Published: May 24, 2021
Biophysical
cues,
such
as
mechanical
properties,
play
a
critical
role
in
tissue
growth
and
homeostasis.
During
organ
development
injury
repair,
compressive
tensional
forces
generated
by
cell-extracellular
matrix
or
cell-cell
interaction
are
key
factors
for
cell
fate
determination.
In
the
vascular
system,
hemodynamic
forces,
shear
stress,
cyclic
stretch
modulate
phenotypes
susceptibility
to
atherosclerosis.
Despite
that
emerging
efforts
have
been
made
investigate
how
mechanotransduction
is
involved
tuning
functions
various
contexts,
regulatory
mechanisms
remain
largely
unknown.
One
of
challenges
understand
signaling
cascades
transmit
cues
from
plasma
membrane
cytoplasm
then
nuclei
generate
mechanoresponsive
transcriptomes.
YAP
its
homolog
TAZ,
Hippo
pathway
effectors,
identified
mechanotransducers
sense
stimuli
relay
signals
control
transcriptional
programs
proliferation,
differentiation,
transformation.
However,
upstream
mechanosensors
YAP/TAZ
downstream
transcriptome
responses
following
activation
repression
not
well
characterized.
Moreover,
mechanoregulation
literature
highly
context-dependent.
this
review,
we
summarize
biomechanical
microenvironment
provide
an
update
on
roles
physiological
pathological
conditions.
Cancer Discovery,
Journal Year:
2023,
Volume and Issue:
13(2), P. 278 - 297
Published: Jan. 9, 2023
Immunotherapies
have
shown
benefits
across
a
range
of
human
cancers,
but
not
pancreatic
ductal
adenocarcinoma
(PDAC).
Recent
evidence
suggests
that
the
immunosuppressive
tumor
microenvironment
(TME)
constitutes
an
important
roadblock
to
their
efficacy.
The
landscape
TME
differs
substantially
PDAC
subtypes,
indicating
context-specific
principles
immunosuppression.
In
this
review,
we
discuss
how
cells,
local
TME,
and
systemic
host
environmental
factors
drive
immunosuppression
in
context.
We
argue
unraveling
mechanistic
drivers
modes
will
open
new
possibilities
target
more
efficiently
by
using
multimodal
(immuno)therapeutic
interventions.
Immunosuppression
is
almost
universal
hallmark
cancer,
although
entity
highly
heterogeneous
its
different
subtypes
phenotypes.
Here,
provide
diverse
cancer
central
executor
various
context-dependent
immunosuppression,
key
challenges
novel
opportunities
uncover,
functionalize,
functional
nodes
for
therapeutic
exploitation.
Materials Today Bio,
Journal Year:
2022,
Volume and Issue:
13, P. 100208 - 100208
Published: Jan. 1, 2022
Nanotechnology
in
medical
applications,
especially
oncology
as
drug
delivery
systems,
has
recently
shown
promising
results.
However,
although
these
advances
have
been
the
pre-clinical
stages,
clinical
translation
of
this
technology
is
challenging.
To
create
systems
with
increased
treatment
efficacy
for
translation,
physicochemical
characteristics
nanoparticles
such
size,
shape,
elasticity
(flexibility/rigidity),
surface
chemistry,
and
charge
can
be
specified
to
optimize
efficiency
a
given
application.
Consequently,
interdisciplinary
researchers
focused
on
producing
biocompatible
materials,
production
technologies,
or
new
formulations
efficient
loading,
high
stability.
The
effects
design
parameters
studied
Cancers,
Journal Year:
2022,
Volume and Issue:
14(12), P. 2868 - 2868
Published: June 10, 2022
The
enhanced
permeability
and
retention
(EPR)
effect
in
cancer
treatment
is
one
of
the
key
mechanisms
that
enables
drug
accumulation
at
tumor
site.
However,
despite
a
plethora
virus/inorganic/organic-based
nanocarriers
designed
to
rely
on
EPR
effectively
target
tumors,
most
have
failed
clinic.
It
seems
non-compliance
research
activities
with
clinical
trials,
goals
unrelated
effect,
lack
awareness
impact
solid
structure
interactions
performance
intensified
this
dissatisfaction.
As
such,
asymmetric
growth
structural
complexity
physicochemical
properties
nanocarriers,
analytical
combination
tools,
description
should
be
considered
improve
EPR-based
therapeutics.
This
review
provides
valuable
insights
into
limitations
therapeutic
efficacy
reports
crucial
perspectives
how
can
modulated
effects
nanomedicine.
Chemical Reviews,
Journal Year:
2023,
Volume and Issue:
123(18), P. 10920 - 10989
Published: Sept. 15, 2023
Anticancer
nanomedicines
have
been
proven
effective
in
mitigating
the
side
effects
of
chemotherapeutic
drugs.
However,
challenges
remain
augmenting
their
therapeutic
efficacy.
Nanomedicines
responsive
to
pathological
abnormalities
tumor
microenvironment
(TME)
are
expected
overcome
biological
limitations
conventional
nanomedicines,
enhance
efficacies,
and
further
reduce
effects.
This
Review
aims
quantitate
various
TME,
which
may
serve
as
unique
endogenous
stimuli
for
design
stimuli-responsive
provide
a
broad
objective
perspective
on
current
understanding
cancer
treatment.
We
dissect
typical
transport
process
barriers
drug
delivery,
highlight
key
principles
designed
tackle
series
delivery
process,
discuss
"all-into-one"
"one-for-all"
strategies
integrating
needed
properties
nanomedicines.
Ultimately,
we
insight
into
future
perspectives
toward
clinical
translation
