Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Июнь 24, 2022
Abstract
Prostate
cancer
(PCa)
affects
millions
of
men
globally.
Due
to
advances
in
understanding
genomic
landscapes
and
biological
functions,
the
treatment
PCa
continues
improve.
Recently,
various
new
classes
agents,
which
include
next-generation
androgen
receptor
(AR)
signaling
inhibitors
(abiraterone,
enzalutamide,
apalutamide,
darolutamide),
bone-targeting
agents
(radium-223
chloride,
zoledronic
acid),
poly(ADP-ribose)
polymerase
(PARP)
(olaparib,
rucaparib,
talazoparib)
have
been
developed
treat
PCa.
Agents
targeting
other
pathways,
including
cyclin-dependent
kinase
(CDK)4/6,
Ak
strain
transforming
(AKT),
wingless-type
protein
(WNT),
epigenetic
marks,
successively
entered
clinical
trials.
Furthermore,
prostate-specific
membrane
antigen
(PSMA)
such
as
177
Lu-PSMA-617
are
promising
theranostics
that
could
improve
both
diagnostic
accuracy
therapeutic
efficacy.
Advanced
studies
with
immune
checkpoint
(ICIs)
shown
limited
benefits
PCa,
whereas
subgroups
mismatch
repair
(MMR)
or
CDK12
inactivation
may
benefit
from
ICIs
treatment.
In
this
review,
we
summarized
targeted
trials
their
underlying
mechanisms,
further
discussed
limitations
future
directions.
Science Signaling,
Год журнала:
2019,
Номер
12(570)
Опубликована: Фев. 26, 2019
Encoded
in
mammalian
cells
by
33
genes,
the
transforming
growth
factor-β
(TGF-β)
family
of
secreted,
homodimeric
and
heterodimeric
proteins
controls
differentiation
most,
if
not
all,
cell
lineages
many
aspects
tissue
physiology
multicellular
eukaryotes.
Deregulation
TGF-β
signaling
leads
to
developmental
anomalies
disease,
whereas
enhanced
contributes
cancer
fibrosis.
Here,
we
review
fundamentals
mechanisms
that
are
initiated
upon
ligand
binding
its
surface
receptors
dependence
responses
on
input
from
cooperation
with
other
pathways.
We
discuss
how
exquisitely
control
functional
presentation
activation
heteromeric
receptor
complexes
transmembrane,
dual-specificity
kinases
and,
thus,
define
their
context-dependent
responsiveness
ligands.
also
introduce
through
which
called
Smads
act
as
intracellular
effectors
ligand-induced
gene
expression
show
specificity
impressive
versatility
Smad
depend
cross-talk
Last,
non-Smad
mechanisms,
distinct
ligand-activated
complexes,
complement
thus
contribute
cellular
responses.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Апрель 23, 2021
Abstract
The
extracellular
matrix
(ECM)
is
one
of
the
major
components
tumors
that
plays
multiple
crucial
roles,
including
mechanical
support,
modulation
microenvironment,
and
a
source
signaling
molecules.
quantity
cross-linking
status
ECM
are
factors
determining
tissue
stiffness.
During
tumorigenesis,
interplay
between
cancer
cells
tumor
microenvironment
(TME)
often
results
in
stiffness
ECM,
leading
to
aberrant
mechanotransduction
further
malignant
transformation.
Therefore,
comprehensive
understanding
dysregulation
TME
would
contribute
discovery
promising
therapeutic
targets
for
treatment.
Herein,
we
summarized
knowledge
concerning
following:
(1)
constituents
their
functions
both
normal
conditions;
(2)
TME;
(3)
key
receptors
alteration
during
carcinogenesis;
(4)
current
strategies
targeting
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Март 10, 2022
Abstract
Although
the
treatment
of
myocardial
infarction
(MI)
has
improved
considerably,
it
is
still
a
worldwide
disease
with
high
morbidity
and
mortality.
Whilst
there
long
way
to
go
for
discovering
ideal
treatments,
therapeutic
strategies
committed
cardioprotection
cardiac
repair
following
ischemia
are
emerging.
Evidence
pathological
characteristics
in
MI
illustrates
cell
signaling
pathways
that
participate
survival,
proliferation,
apoptosis,
autophagy
cardiomyocytes,
endothelial
cells,
fibroblasts,
monocytes,
stem
cells.
These
include
key
players
inflammation
response,
e.g.,
NLRP3/caspase-1
TLR4/MyD88/NF-κB;
crucial
mediators
oxidative
stress
instance,
Notch,
Hippo/YAP,
RhoA/ROCK,
Nrf2/HO-1,
Sonic
hedgehog;
controller
fibrosis
such
as
TGF-β/SMADs
Wnt/β-catenin;
main
regulator
angiogenesis,
PI3K/Akt,
MAPK,
JAK/STAT,
hedgehog,
etc.
Since
play
an
important
role
administering
process
MI,
aiming
at
targeting
these
aberrant
improving
manifestations
indispensable
promising.
Hence,
drug
therapy,
gene
protein
exosome
therapy
have
been
emerging
known
novel
therapies.
In
this
review,
we
summarize
by
regulating
associated
pathways,
which
contribute
inhibiting
cardiomyocytes
death,
attenuating
inflammation,
enhancing
so
re-functionalize
damaged
hearts.
Journal of the American College of Cardiology,
Год журнала:
2019,
Номер
73(2), С. 190 - 209
Опубликована: Янв. 1, 2019
Endothelial
to
mesenchymal
transition
(EndMT)
is
a
process
whereby
an
endothelial
cell
undergoes
series
of
molecular
events
that
lead
change
in
phenotype
toward
(e.g.,
myofibroblast,
smooth
muscle
cell).
EndMT
plays
fundamental
role
during
development,
and
mounting
evidence
indicates
involved
adult
cardiovascular
diseases
(CVDs),
including
atherosclerosis,
pulmonary
hypertension,
valvular
disease,
fibroelastosis.
Therefore,
the
targeting
may
hold
therapeutic
promise
for
treating
CVD.
However,
field
faces
number
challenges,
lack
precise
functional
definition,
understanding
causative
pathological
CVDs
(versus
being
“bystander-phenomenon”),
robust
human
data
corroborating
extent
causality
CVDs.
Here,
we
review
this
emerging
but
exciting
field,
propose
framework
its
systematic
advancement
at
translational
levels.
Cold Spring Harbor Perspectives in Biology,
Год журнала:
2017,
Номер
10(2), С. a022210 - a022210
Опубликована: Март 27, 2017
Marie-José
Goumans
and
Peter
ten
Dijke
Department
of
Molecular
Cell
Biology
Cancer
Genomics
Centre
Netherlands,
Leiden
University
Medical
Center,
2300
RC
Leiden,
The
Netherlands
Correspondence:
m.j.t.h.goumans{at}lumc.nl
