Cancers,
Год журнала:
2018,
Номер
10(1), С. 23 - 23
Опубликована: Янв. 19, 2018
The
mammalian
Target
of
Rapamycin
(mTOR)
pathway
plays
an
essential
role
in
sensing
and
integrating
a
variety
exogenous
cues
to
regulate
cellular
growth
metabolism,
both
physiological
pathological
conditions.
mTOR
functions
through
two
functionally
structurally
distinct
multi-component
complexes,
mTORC1
mTORC2,
which
interact
with
each
other
several
elements
signaling
pathways.
In
the
past
few
years,
many
new
insights
into
function
regulation
have
been
gained
extensive
genetic
pharmacological
studies
mice
enhanced
our
understanding
how
dysfunction
contributes
diseases,
including
cancer.
Single-agent
targeting,
mostly
using
rapalogs,
has
so
far
met
limited
clinical
success;
however,
due
cross-talk
between
pathways,
combined
approaches
are
most
promising
avenues
improve
efficacy
available
therapeutics
overcome
drug
resistance.
This
review
provides
brief
up-to-date
narrative
on
function,
relative
contributions
mTORC2
complexes
cancer
development
progression,
prospects
for
inhibition
as
therapeutic
strategy.
Cell Research,
Год журнала:
2020,
Номер
30(6), С. 507 - 519
Опубликована: Май 28, 2020
Abstract
Immunotherapy
holds
the
potential
to
induce
durable
responses,
but
only
a
minority
of
patients
currently
respond.
The
etiologies
primary
and
secondary
resistance
immunotherapy
are
multifaceted,
deriving
not
from
tumor
intrinsic
factors,
also
complex
interplay
between
cancer
its
microenvironment.
In
addressing
frontiers
in
clinical
immunotherapy,
we
describe
two
categories
approaches
design
novel
drugs
combination
therapies:
first
involves
direct
modification
tumor,
while
second
indirectly
enhances
immunogenicity
through
alteration
By
systematically
factors
that
mediate
resistance,
able
identify
mechanistically-driven
improve
outcomes.
International Journal of Molecular Sciences,
Год журнала:
2019,
Номер
20(3), С. 755 - 755
Опубликована: Фев. 11, 2019
The
mammalian
or
mechanistic
target
of
rapamycin
(mTOR)
pathway
plays
a
crucial
role
in
regulation
cell
survival,
metabolism,
growth
and
protein
synthesis
response
to
upstream
signals
both
normal
physiological
pathological
conditions,
especially
cancer.
Aberrant
mTOR
signaling
resulting
from
genetic
alterations
different
levels
the
signal
cascade
is
commonly
observed
various
types
cancers.
Upon
hyperactivation,
promotes
proliferation
metabolism
that
contribute
tumor
initiation
progression.
In
addition,
also
negatively
regulates
autophagy
via
ways.
We
discuss
its
key
downstream
factors,
specific
changes
inhibitors
applied
as
therapeutic
strategies
eight
solid
tumors.
Although
monotherapy
combination
therapy
with
have
been
extensively
preclinical
clinical
trials
cancer
types,
innovative
therapies
better
efficacy
less
drug
resistance
are
still
great
need,
new
biomarkers
deep
sequencing
technologies
will
facilitate
these
targeting
drugs
benefit
patients
personalized
therapy.
Frontiers in Oncology,
Год журнала:
2022,
Номер
12
Опубликована: Март 24, 2022
Cancer
is
a
severe
public
health
issue
that
leading
cause
of
mortality
globally.
It
also
an
impediment
to
improving
life
expectancy
worldwide.
Furthermore,
the
global
burden
cancer
incidence
and
death
continuously
growing.
Current
therapeutic
options
are
insufficient
for
patients,
tumor
complexity
heterogeneity
necessitate
customized
medicine
or
targeted
therapy.
critical
identify
potential
targets.
Aberrant
activation
PI3K/AKT/mTOR
pathway
has
significant
role
in
carcinogenesis.
This
review
summarized
oncogenic
PI3K/Akt/mTOR
alterations
various
hallmarks
associated
with
pathway,
such
as
cell
proliferation,
autophagy,
apoptosis,
angiogenesis,
epithelial-to-mesenchymal
transition
(EMT),
chemoresistance.
Importantly,
this
provided
recent
advances
inhibitor
research.
Overall,
in-depth
understanding
association
between
tumorigenesis
development
therapies
targeting
will
help
make
clinical
decisions.
International Journal of Molecular Sciences,
Год журнала:
2020,
Номер
21(12), С. 4507 - 4507
Опубликована: Июнь 25, 2020
Oncogenic
activation
of
the
phosphatidylinositol-3-kinase
(PI3K),
protein
kinase
B
(PKB/AKT),
and
mammalian
target
rapamycin
(mTOR)
pathway
is
a
frequent
event
in
prostate
cancer
that
facilitates
tumor
formation,
disease
progression
therapeutic
resistance.
Recent
discoveries
indicate
complex
crosstalk
between
PI3K-AKT-mTOR
multiple
interacting
cell
signaling
cascades
can
further
promote
influence
sensitivity
cells
to
PI3K-AKT-mTOR-targeted
therapies
being
explored
clinic,
as
well
standard
treatment
approaches
such
androgen-deprivation
therapy
(ADT).
However,
full
extent
network
during
tumorigenesis,
invasive
recurrence
remains
be
determined.
In
this
review,
we
outline
emerging
diversity
genetic
alterations
lead
activated
cancer,
discuss
new
mechanistic
insights
into
interplay
several
key
oncogenic
cooperate
facilitate
growth
drug-resistance,
specifically
androgen
receptor
(AR),
mitogen-activated
(MAPK),
WNT
cascades.
Ultimately,
deepening
our
understanding
broader
crucial
aid
patient
stratification
for
pathway-directed
therapies,
discover
improve
outcome.
