Background:
Glioblastoma
(GBM)
is
the
most
common
primary
brain
malignant
tumor
and
one
of
lethal
human
cancers
with
very
limited
effective
therapeutics.
A
few
neoantigens
that
have
been
tested
in
trials
as
cancer
immunotherapeutic
vaccines
against
GBM
demonstrated
promising
but
ambiguous
results.
However,
there
no
systemic
exploration
neoantigen
landscape
its
related
microenvironment.Methods:
An
integrated
multi-omic
approach
consisting
WES,
RNA
sequencing,
bioinformatic
algorisms
was
applied
to
comprehensively
profile
mutation,
HLA
typing,
TCR/BCR
repertoire,
immune
cell
components
on
tissue
peripheral
blood
mononuclear
(PMBC)
specimen
24
patients.
The
characterized
a
cluster
peptides
designed
for
this
patient
cohort.Findings:
On
average,
148
mutated
genes
200
sites
per
were
identified,
predominant
cohort.
Diversified
genotypes
expression
rate
across
A,
B,
C
alleles,
A30:01&A11:01,
B13:02,
C06:02,
frequent
at
respective
alleles.
Clustered
CDR3
existed
decreased
richness
compared
PMBC.
NKT
Th1
cells
revealed
within
TMB.
Neoantigens
feasible
predicted
each
patient,
an
average
number
107.
Very
shared
by
more
than
two
patients
dominant
could
be
identified.
minimum
11-peptide
bulk
required
cover
24-patient
cohort,
guaranteeing
least
neoantigen.Interpretation:
Our
study
reveals
inherent
TME
heterogeneous
immunogenic
signatures,
which
should
facilitate
optimized
design
therapeutic
terms
target
selection
strategy.Funding:
This
received
support
from
Beijing
Municipal
Nature
Science
Foundation
(Grant
No.
Z191100007619018).Declaration
Interest:
authors
declare
competing
interests.Ethical
Approval:
All
provided
written
informed
consent
sample
collection
data
analyses.
approved
Ethical
Committee
Xuanwu
Hospital,
Beijing,
China.
Abstract
Chemodynamic
therapy
(CDT)
has
shown
promising
antitumor
effects
in
various
malignant
tumors.
However,
its
application
for
glioblastoma
(GBM)
is
significantly
hindered
by
the
challenge
of
delivering
CDT
agents
across
blood‐brain
barrier
(BBB)
and
achieving
efficient
tumor
targeting.
To
overcome
these
obstacles,
this
study
presents
a
novel
DNA
nanomachine
(Cu@tFNAs‐G‐A
NM)
loading
copper
ions
(Cu
2+
)
onto
tetrahedral
framework
nucleic
acids
(tFNAs)
functionalized
with
dual
aptamers.
The
aptamers
(GS24
BBB
penetration
AS1411
targeting)
empowered
Cu@tFNAs‐G‐A
NM
ability
to
effectively
penetrate
selectively
accumulate
cells.
Upon
internalization,
loaded
Cu
reacted
tumor‐overexpressed
reductive
glutathione
(GSH)
hydrogen
peroxide
(H
2
O
),
generating
hydroxyl
radicals
(·OH)
inducing
cell
death.
Additionally,
was
found
be
rapidly
cleared
from
brain
normal
tissues
within
24
h,
minimizing
potential
systemic
toxic
side
effects.
These
findings
demonstrate
effective
against
GBM
open
up
new
avenues
development
targeted
therapies
GBM.
Cells,
Год журнала:
2024,
Номер
13(4), С. 336 - 336
Опубликована: Фев. 13, 2024
Glioblastoma
(GB)
is
a
rare
but
extremely
aggressive
brain
tumor
that
significantly
impacts
patient
outcomes,
affecting
both
duration
and
quality
of
life.
The
protocol
established
by
Stupp
colleagues
in
2005,
based
on
radiotherapy
chemotherapy
with
Temozolomide,
following
maximum
safe
surgical
resection
remains
the
gold
standard
for
GB
treatment;
however,
it
evident
nowadays
extreme
intratumoral
intertumoral
heterogeneity,
as
well
invasiveness
tendency
to
recur,
are
not
compatible
routine
unfortunately
ineffective
treatment.
This
review
article
summarizes
main
challenges
search
new
valuable
therapies
focuses
impact
extracellular
vesicle
(EV)
research
exploitation
may
have
field.
EVs
natural
particles
delimited
lipidic
bilayer
filled
functional
cellular
content
released
uptaken
cells
key
means
cell
communication.
Furthermore,
stable
body
fluids
tolerated
immune
system,
able
cross
physiological,
interspecies,
interkingdom
barriers
target
specific
cells,
releasing
inherent
or
externally
loaded
functionally
active
molecules.
Therefore,
potential
be
ideal
allies
fight
against
improve
prognosis
patients.
present
work
describes
preclinical
results
obtained
so
far
use
treatment,
focusing
EV
sources
molecular
cargo
used
various
studies,
primarily
vivo.
Finally,
SWOT
analysis
performed,
highlighting
advantages
pitfalls
developing
EV-based
therapeutic
strategies.
also
suggests
directions
explore
realize
possibility
exploiting
treatment
GB.
Cancers,
Год журнала:
2024,
Номер
16(11), С. 2089 - 2089
Опубликована: Май 30, 2024
Background:
The
study
aims
to
investigate
the
role
of
hypoxia-inducible
factors
(HIFs)
in
development,
progression,
and
therapeutic
potential
glioblastomas.
Methodology:
study,
following
PRISMA
guidelines,
systematically
examined
hypoxia
HIFs
glioblastoma
using
MEDLINE
(PubMed),
Web
Science,
Scopus.
A
total
104
relevant
studies
underwent
data
extraction.
Results:
Among
studies,
global
contributions
were
diverse,
with
China
leading
at
23.1%.
most
productive
year
was
2019,
accounting
for
11.5%.
Hypoxia-inducible
factor
1
alpha
(HIF1α)
frequently
studied,
followed
by
2
(HIF2α),
osteopontin,
cavolin-1.
Commonly
associated
pathways
include
glucose
transporter
(GLUT1)
3
(GLUT3)
receptors,
vascular
endothelial
growth
(VEGF),
phosphoinositide
3-kinase
(PI3K)-Akt-mechanistic
target
rapamycin
(mTOR)
pathway,
reactive
oxygen
species
(ROS).
HIF
expression
correlates
various
hallmarks,
including
survival,
neovascularization,
metabolism,
migration,
invasion.
Conclusion:
Overcoming
challenges
such
as
treatment
resistance
absence
biomarkers
is
critical
effective
integration
HIF-related
therapies
into
aim
optimizing
patient
outcomes.
Frontiers in Oncology,
Год журнала:
2025,
Номер
15
Опубликована: Март 21, 2025
Introduction
Glioblastoma
(GBM)
is
the
most
common
primary
brain
malignancy.
Few
neoantigens
have
been
tested
in
trials
as
cancer
vaccine
against
GBM.
Methods
To
better
understand
neoantigen
landscape
and
its
associated
tumor
microenvironment
(TME)
for
optimized
design
of
our
initiated
GBM
trial,
we
apply
integrative
multi-omics
approach
to
comprehensively
profile
mutation,
HLA
typing,
TCR/BCR
repertoire,
immune
cell
components
on
tissue
peripheral
blood
mononuclear
(PMBC)
specimen
24
patients.
Results
On
average,
148
mutated
genes
200
sites
per
patient
were
identified,
with
no
predominant
this
cohort.
Diversified
genotypes
expression
rate
across
A,
B,
C
alleles,
A30:01&A11:01,
B13:02,
C06:02,
frequent
at
respective
alleles.
Clustered
CDR3
existed
decreased
richness
compared
PMBC.
NK
Th1
cells
revealed
within
(TME).
Neoantigens
feasible
predicted
designed
each
patient,
an
average
number
107.
Very
few
shared
by
more
than
two
patients
dominant
could
be
identified.
A
minimum
11-peptide
bulk
was
required
cover
24-patient
cohort,
guaranteeing
least
one
neoantigen.
Discussion
In
summary,
data
reveals
a
heterogeneous
TME
GBM,
based
which
peptide
feasibly
developed
these
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(7), С. 3283 - 3283
Опубликована: Апрель 1, 2025
Medical
treatment
of
glioblastoma
presents
a
significant
challenge.
A
conventional
medication
has
limited
effectiveness,
and
single-target
therapy
is
usually
effective
only
in
the
early
stage
treatment.
Recently,
there
been
increasing
focus
on
multi-target
therapies,
but
vast
range
possible
combinations
makes
clinical
experimentation
implementation
difficult.
From
perspective
systems
biology,
this
study
conducted
simulations
for
based
dynamic
analysis
previously
established
endogenous
networks,
validated
with
single-cell
RNA
sequencing
data.
Several
potentially
target
were
identified.
The
findings
also
highlight
necessity
rather
than
intervention
strategies
cancer
treatment,
as
well
promise
applications
personalized
therapies.
Cancers,
Год журнала:
2023,
Номер
16(1), С. 102 - 102
Опубликована: Дек. 24, 2023
Glioblastoma
multiforme
(GBM)
represents
a
diverse
spectrum
of
primary
tumors
notorious
for
their
resistance
to
established
therapeutic
modalities.
Despite
aggressive
interventions
like
surgery,
radiation,
and
chemotherapy,
these
tumors,
due
factors
such
as
the
blood–brain
barrier,
tumor
heterogeneity,
glioma
stem
cells
(GSCs),
drug
efflux
pumps,
DNA
damage
repair
mechanisms,
persist
beyond
complete
isolation,
resulting
in
dismal
outcomes
patients.
Presently,
standard
initial
approach
comprises
surgical
excision
followed
by
concurrent
where
temozolomide
(TMZ)
serves
foremost
option
managing
GBM
Subsequent
adjuvant
chemotherapy
follows
this
regimen.
Emerging
approaches
encompass
immunotherapy,
including
checkpoint
inhibitors,
targeted
treatments,
bevacizumab,
aiming
exploit
vulnerabilities
within
cells.
Nevertheless,
there
exists
pressing
imperative
devise
innovative
strategies
both
diagnosing
treating
GBM.
This
review
emphasizes
current
knowledge
GSC
biology,
molecular
associations
with
various
signals
and/or
pathways,
epidermal
growth
factor
receptor,
PI3K/AKT/mTOR,
HGFR/c-MET,
NF-κB,
Wnt,
Notch,
STAT3
pathways.
Metabolic
reprogramming
GSCs
has
also
been
reported
prominent
activation
glycolytic
pathway,
comprising
aldehyde
dehydrogenase
family
genes.
We
discuss
potential
targets
currently
used
well
mode
action
on
targets.