Abstract
T
cells
engineered
to
express
chimeric
antigen
receptors
(CARs)
with
specificity
toward
tumor
have
led
promising
outcomes
in
patients
hematological
malignancies.
Nevertheless,
the
application
of
CAR‐T
cell
therapy
solid
tumors
encounters
several
obstacles.
These
include
heterogeneity
and
immune
escape,
exhaustion
restricted
infiltration
into
that
affect
therapeutic
efficacy
cells,
as
well
“on‐target,
off‐tumor”
toxicities
can
lead
severe
even
fatal
adverse
events.
In
recent
years,
clinical
trials
new
approaches
for
made
certain
progress.
Here,
we
update
related
summarize
strategies
aiming
improve
safety
based
on
experimental
studies.
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Фев. 12, 2024
Abstract
Cancer
treatment
faces
many
hurdles
and
resistance
is
one
among
them.
Anti-cancer
strategies
are
evolving
due
to
innate
acquired
capacity,
governed
by
genetic,
epigenetic,
proteomic,
metabolic,
or
microenvironmental
cues
that
ultimately
enable
selected
cancer
cells
survive
progress
under
unfavorable
conditions.
Although
the
mechanism
of
drug
being
widely
studied
generate
new
target-based
drugs
with
better
potency
than
existing
ones.
However,
broader
flexibility
in
resistance,
advanced
therapeutic
options
efficacy
need
be
explored.
Combination
therapy
an
alternative
a
success
rate
though
risk
amplified
side
effects
commonplace.
Moreover,
recent
groundbreaking
precision
immune
ways
overcome
has
revolutionized
anticancer
greater
extent
only
limitation
individual-specific
needs
further
attention.
This
review
will
focus
on
challenges
opted
withstand
current
therapies
at
molecular
level
also
highlights
emerging
-like
immunological,
stem
cell-based
may
prove
have
potential
challenge
problem
resistance.
Advanced Materials,
Год журнала:
2022,
Номер
35(21)
Опубликована: Ноя. 29, 2022
Abstract
Emerging
as
a
potent
anticancer
treatment,
subcellular
targeted
cancer
therapy
has
drawn
increasing
attention,
bringing
great
opportunities
for
clinical
application.
Here,
two
targeting
strategies
four
main
organelles
(mitochondria,
lysosome,
endoplasmic
reticulum,
and
nucleus),
including
molecule‐
nanomaterial
(inorganic
nanoparticles,
micelles,
organic
polymers,
others)‐based
delivery
or
therapeutic
strategies,
are
summarized.
Phototherapy,
chemotherapy,
radiotherapy,
immunotherapy,
“all‐in‐one”
combination
among
the
covered
in
detail.
Such
materials
constructed
based
on
specific
properties
relevant
mechanisms
of
organelles,
enabling
elimination
tumors
by
inducing
dysfunction
corresponding
destroying
structures.
The
challenges
faced
organelle‐targeting
therapies
also
Looking
forward,
paradigm
with
enhanced
efficacy
compared
to
current
approaches
is
envisioned.
Trends in cancer,
Год журнала:
2023,
Номер
9(11), С. 937 - 954
Опубликована: Авг. 8, 2023
During
tumor
progression,
mechanical
abnormalities
in
the
microenvironment
(TME)
trigger
signaling
pathways
cells
that
activate
cellular
programs,
resulting
growth
and
drug
resistance.
In
this
review,
we
describe
mechanisms
of
action
for
anti-cancer
therapies
mechanotransduction
programs
regulate
processes,
including
cell
proliferation,
apoptosis,
survival
phenotype
switching.
We
discuss
how
therapeutic
response
is
impacted
by
three
main
TME
abnormalities:
high
extracellular
matrix
(ECM)
composition
stiffness;
interstitial
fluid
pressure
(IFP);
elevated
forces.
also
review
drugs
normalize
these
or
block
mechanosensors
pathways.
Finally,
current
challenges
perspectives
development
new
strategies
targeting
mechanically
induced
resistance
clinic.
Cancer Discovery,
Год журнала:
2023,
Номер
13(4), С. 880 - 909
Опубликована: Янв. 26, 2023
Blocking
cancer
genomic
instability
may
prevent
tumor
diversification
and
escape
from
therapies.
We
show
that,
after
MAPK
inhibitor
(MAPKi)
therapy
in
patients
mice
bearing
patient-derived
xenografts
(PDX),
acquired
resistant
genomes
of
metastatic
cutaneous
melanoma
specifically
amplify
resistance-driver,
nonhomologous
end-joining
(NHEJ),
homologous
recombination
repair
(HRR)
genes
via
complex
rearrangements
(CGR)
extrachromosomal
DNAs
(ecDNA).
Almost
all
sensitive
acquired-resistant
harbor
pervasive
chromothriptic
regions
with
disproportionately
high
mutational
burdens
significant
overlaps
ecDNA
CGR
spans.
Recurrently,
somatic
mutations
within
amplicons
enrich
for
HRR
signatures,
particularly
tumors.
Regardless
sensitivity
or
resistance,
breakpoint-junctional
sequence
analysis
suggests
NHEJ
as
critical
to
double-stranded
DNA
break
underlying
formation.
In
human
cell
lines
PDXs,
targeting
by
a
DNA-PKCS
prevents/delays
MAPKi
resistance
reducing
the
size
ecDNAs
CGRs
early
on
combination
treatment.
Thus,
causes
prevents
resistance.
Acquired
often
results
heterogeneous,
redundant
survival
mechanisms,
which
challenge
strategies
aimed
at
reversing
Acquired-resistant
melanomas
recurrently
evolve
resistance-driving
resistance-specific
CGRs,
thereby
nominating
chromothripsis-ecDNA-CGR
biogenesis
resistance-preventive
target.
Specifically,
DNA-PKCS/NHEJ
suppressing
ecDNA/CGR
MAPKi-treated
melanomas.
This
article
is
highlighted
Issue
feature,
p.
799.
Journal of Translational Medicine,
Год журнала:
2024,
Номер
22(1)
Опубликована: Янв. 3, 2024
Abstract
Breast
cancer
(BC)
is
a
multifaceted
disease
characterized
by
distinct
molecular
subtypes
and
varying
responses
to
treatment.
In
BC,
the
phosphatidylinositol
3-kinase
(PI3K)
pathway
has
emerged
as
crucial
contributor
development,
advancement,
resistance
This
review
article
explores
implications
of
PI3K
in
predictive,
preventive,
personalized
medicine
for
BC.
It
emphasizes
identification
predictive
biomarkers,
such
PIK3CA
mutations,
utility
profiling
guiding
treatment
decisions.
The
also
discusses
potential
targeting
preventive
strategies
customization
therapy
based
on
tumor
stage,
subtypes,
genetic
alterations.
Overcoming
inhibitors
exploring
combination
therapies
are
addressed
important
considerations.
While
this
field
holds
promise
improving
patient
outcomes,
further
research
clinical
trials
needed
validate
these
approaches
translate
them
into
practice.
Graphical
Cancer Discovery,
Год журнала:
2024,
Номер
14(5), С. 766 - 785
Опубликована: Фев. 6, 2024
Adding
anti-programmed
cell
death
protein
1
(anti-PD-1)
to
5-fluorouracil
(5-FU)/platinum
improves
survival
in
some
advanced
gastroesophageal
adenocarcinomas
(GEA).
To
understand
the
effects
of
chemotherapy
and
immunotherapy,
we
conducted
a
phase
II
first-line
trial
(n
=
47)
sequentially
adding
pembrolizumab
5-FU/platinum
GEA.
Using
serial
biopsy
primary
tumor
at
baseline,
after
one
cycle
5-FU/platinum,
addition
pembrolizumab,
transcriptionally
profiled
358,067
single
cells
identify
evolving
multicellular
microenvironment
(TME)
networks.
Chemotherapy
induced
early
on-treatment
hubs
with
tumor-reactive
T-cell
M1-like
macrophage
interactions
slow
progressors.
Faster
progression
featured
increased
MUC5A
MSLN
containing
treatment
resistance
programs
M2-like
macrophages
immunosuppressive
stromal
interactions.
After
observed
CD8
infiltration
development
an
immunity
hub
involving
CXCL13
program
epithelial
interferon-stimulated
gene
programs.
Strategies
drive
increases
antitumor
immune
formation
could
expand
portion
patients
benefiting
from
anti-PD-1
approaches.
