Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Авг. 28, 2023
Abstract
Immune-checkpoint
inhibitors
(ICBs),
in
addition
to
targeting
CTLA-4,
PD-1,
and
PD-L1,
novel
LAG-3
drugs
have
also
been
approved
clinical
application.
With
the
widespread
use
of
drug,
we
must
deeply
analyze
dilemma
agents
seek
a
breakthrough
treatment
prospect.
Over
past
decades,
these
demonstrated
dramatic
efficacy,
especially
patients
with
melanoma
non-small
cell
lung
cancer
(NSCLC).
Nonetheless,
field
broad
concept
solid
tumours,
non-specific
indications,
inseparable
immune
response
side
effects,
unconfirmed
progressive
disease,
complex
regulatory
networks
resistance
are
four
barriers
that
limit
its
Fortunately,
successful
trials
ICB
combination
therapies,
advent
era
oncolytic
virus
gene
editing,
technical
mRNA
vaccines
nano-delivery
systems
made
remarkable
breakthroughs
currently.
In
this
review,
enumerate
mechanisms
each
checkpoint
targets,
associations
between
tumour
mutation
burden,
key
or
signalling
pathways,
specific
evidence
efficacy
classical
targets
new
among
different
types
put
forward
dialectical
thoughts
on
drug
safety.
Finally,
discuss
importance
accurate
triage
based
recent
advances
predictive
biomarkers
diagnostic
testing
techniques.
Cancer Discovery,
Год журнала:
2022,
Номер
12(1), С. 31 - 46
Опубликована: Янв. 1, 2022
The
hallmarks
of
cancer
conceptualization
is
a
heuristic
tool
for
distilling
the
vast
complexity
phenotypes
and
genotypes
into
provisional
set
underlying
principles.
As
knowledge
mechanisms
has
progressed,
other
facets
disease
have
emerged
as
potential
refinements.
Herein,
prospect
raised
that
phenotypic
plasticity
disrupted
differentiation
discrete
hallmark
capability,
nonmutational
epigenetic
reprogramming
polymorphic
microbiomes
both
constitute
distinctive
enabling
characteristics
facilitate
acquisition
capabilities.
Additionally,
senescent
cells,
varying
origins,
may
be
added
to
roster
functionally
important
cell
types
in
tumor
microenvironment.
SIGNIFICANCE:
Cancer
daunting
breadth
scope
its
diversity,
spanning
genetics,
tissue
biology,
pathology,
response
therapy.
Ever
more
powerful
experimental
computational
tools
technologies
are
providing
an
avalanche
"big
data"
about
myriad
manifestations
diseases
encompasses.
integrative
concept
embodied
helping
distill
this
increasingly
logical
science,
new
dimensions
presented
perspective
add
value
endeavor,
fully
understand
development
malignant
progression,
apply
medicine.
Cancer Discovery,
Год журнала:
2021,
Номер
11(4), С. 933 - 959
Опубликована: Апрель 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.
Antibodies
targeting
programmed
cell
death
protein-1
(PD-1)
or
its
ligand
PD-L1
rescue
T
cells
from
exhausted
status
and
revive
immune
response
against
cancer
cells.
Based
on
the
immense
success
in
clinical
trials,
ten
α-PD-1
(nivolumab,
pembrolizumab,
cemiplimab,
sintilimab,
camrelizumab,
toripalimab,
tislelizumab,
zimberelimab,
prolgolimab,
dostarlimab)
three
α-PD-L1
antibodies
(atezolizumab,
durvalumab,
avelumab)
have
been
approved
for
various
types
of
cancers.
Nevertheless,
low
rate
α-PD-1/PD-L1
therapy
remains
to
be
resolved.
For
most
patients,
PD-1/PD-L1
pathway
is
not
sole
speed-limiting
factor
antitumor
immunity,
it
insufficient
motivate
effective
by
blocking
axis.
It
has
validated
that
some
combination
therapies,
including
plus
chemotherapy,
radiotherapy,
angiogenesis
inhibitors,
targeted
therapy,
other
checkpoint
agonists
co-stimulatory
molecule,
stimulator
interferon
genes
agonists,
fecal
microbiota
transplantation,
epigenetic
modulators,
metabolic
superior
efficacies
higher
rates.
Moreover,
bifunctional
bispecific
containing
moiety
also
elicited
more
potent
activity.
These
strategies
simultaneously
boost
multiple
processes
cancer-immunity
cycle,
remove
immunosuppressive
brakes,
orchestrate
an
immunosupportive
tumor
microenvironment.
In
this
review,
we
summarized
synergistic
mechanisms
with
therapies.
focused
advances
α-PD-1/PD-L1-based
immunomodulatory
studies.
Given
heterogeneity
across
patients
types,
individualized
selection
could
improve
effects
relieve
treatment
resistance.
Microbial
roles
in
cancer
formation,
diagnosis,
prognosis,
and
treatment
have
been
disputed
for
centuries.
Recent
studies
provocatively
claimed
that
bacteria,
viruses,
and/or
fungi
are
pervasive
among
cancers,
key
actors
immunotherapy,
engineerable
to
treat
metastases.
Despite
these
findings,
the
number
of
microbes
known
directly
cause
carcinogenesis
remains
small.
Critically
evaluating
building
frameworks
such
evidence
light
modern
biology
is
an
important
task.
In
this
Review,
we
delineate
between
causal
complicit
trace
common
themes
their
influence
through
host's
immune
system,
herein
defined
as
immuno-oncology-microbiome
axis.
We
further
review
intratumoral
approaches
manipulate
gut
or
tumor
microbiome
while
projecting
next
phase
experimental
discovery.
Science,
Год журнала:
2021,
Номер
374(6575), С. 1632 - 1640
Опубликована: Дек. 23, 2021
Gut
bacteria
modulate
the
response
to
immune
checkpoint
blockade
(ICB)
treatment
in
cancer,
but
effect
of
diet
and
supplements
on
this
interaction
is
not
well
studied.
We
assessed
fecal
microbiota
profiles,
dietary
habits,
commercially
available
probiotic
supplement
use
melanoma
patients
performed
parallel
preclinical
studies.
Higher
fiber
was
associated
with
significantly
improved
progression-free
survival
128
ICB,
most
pronounced
benefit
observed
sufficient
intake
no
use.
Findings
were
recapitulated
models,
which
demonstrated
impaired
anti–programmed
cell
death
1
(anti–PD-1)–based
therapy
mice
receiving
a
low-fiber
or
probiotics,
lower
frequency
interferon-γ–positive
cytotoxic
T
cells
tumor
microenvironment.
Together,
these
data
have
clinical
implications
for
ICB
cancer.
