Recent Treatment Strategies and Molecular Pathways in Resistance Mechanisms of Antiangiogenic Therapies in Glioblastoma
Cancers,
Год журнала:
2024,
Номер
16(17), С. 2975 - 2975
Опубликована: Авг. 27, 2024
Malignant
gliomas
present
great
difficulties
in
treatment,
with
little
change
over
the
past
30
years
median
survival
time
of
15
months.
Current
treatment
options
include
surgery,
radiotherapy
(RT),
and
chemotherapy.
New
therapies
aimed
at
suppressing
formation
new
vasculature
(antiangiogenic
treatments)
or
destroying
formed
tumor
(vascular
disrupting
agents)
show
promise.
This
study
summarizes
existing
knowledge
regarding
processes
by
which
glioblastoma
(GBM)
tumors
acquire
resistance
to
antiangiogenic
treatments.
The
discussion
encompasses
activation
redundant
proangiogenic
pathways,
heightened
cell
invasion
metastasis,
induced
hypoxia,
creation
vascular
mimicry
channels,
regulation
immune
microenvironment.
Subsequently,
we
explore
potential
strategies
overcome
this
resistance,
such
as
combining
other
methods,
personalizing
treatments
for
each
patient,
focusing
on
therapeutic
targets,
incorporating
immunotherapy,
utilizing
drug
delivery
systems
based
nanoparticles.
Additionally,
would
like
discuss
limitations
methods
future
directions
enhance
beneficial
effects
patients
GBM.
Therefore,
review
aims
research
outcome
GBM
provide
a
more
promising
opportunity
thoroughly
exploring
mechanisms
investigating
novel
strategies.
Язык: Английский
High costs, low quality of life, reduced survival, and room for improving treatment: an analysis of burden and unmet needs in glioma
Frontiers in Oncology,
Год журнала:
2024,
Номер
14
Опубликована: Март 20, 2024
Gliomas
are
a
group
of
heterogeneous
tumors
that
account
for
substantial
morbidity,
mortality,
and
costs
to
patients
healthcare
systems
globally.
Survival
varies
considerably
by
grade,
histology,
biomarkers,
genetic
alterations
such
as
IDH
mutations
MGMT
promoter
methylation,
treatment,
but
is
poor
some
grades
histologies,
with
many
glioblastoma
surviving
less
than
year
from
diagnosis.
The
present
review
provides
an
introduction
glioma,
including
its
classification,
epidemiology,
economic
humanistic
burden,
well
treatment
options.
Another
focus
on
recommendations
IDH-mutant
astrocytoma,
oligodendroglioma,
glioblastoma,
which
were
synthesized
recent
guidelines.
While
nuanced
reflect
the
complexity
disease,
maximum
safe
resection
typically
first
step
in
followed
radiotherapy
and/or
chemotherapy
using
temozolomide
or
procarbazine,
lomustine,
vincristine.
Immunotherapies
targeted
therapies
currently
have
only
limited
role
due
disappointing
clinical
trial
results,
recurrent
nitrosourea
lomustine
remains
de
facto
standard
care.
lack
options
compounded
frequently
suboptimal
practice,
do
not
receive
adequate
therapy
after
resection,
delayed,
shortened,
discontinued
courses
side
effects.
These
unmet
needs
will
require
significant
efforts
address,
continued
search
novel
options,
increased
awareness
guidelines,
improved
toxicity
management
chemotherapy,
generation
additional
more
robust
health
evidence.
Язык: Английский
Cell membrane sialome machinery and regulation of receptor tyrosine kinases in gliomas: The functional relevance and therapeutic perspectives
Biomedicine & Pharmacotherapy,
Год журнала:
2025,
Номер
184, С. 117921 - 117921
Опубликована: Фев. 21, 2025
Язык: Английский
Chitosan-Coated Liposome Formulations for Encapsulation of Ciprofloxacin and Etoposide
Pharmaceutics,
Год журнала:
2024,
Номер
16(8), С. 1036 - 1036
Опубликована: Авг. 2, 2024
Cancer
and
bacterial
infections
rank
among
the
most
significant
global
health
threats.
accounting
for
roughly
25
million
fatalities
each
year.
This
statistic
underscores
urgent
necessity
developing
novel
drugs,
enhancing
current
treatments,
implementing
systems
that
boost
their
bioavailability
to
achieve
superior
therapeutic
outcomes.
Liposomes
have
been
recognised
as
effective
carriers;
nonetheless,
they
encounter
issues
with
long-term
stability
structural
integrity,
which
limit
pharmaceutical
applicability.
Chitosomes
(chitosan-coated
liposomes)
are
generally
a
good
alternative
solve
these
issues.
research
aims
demonstrate
individual
encapsulation
of
ciprofloxacin
(antibacterial,
hydrophilic)
etoposide
(anticancer,
hydrophobic),
within
chitosomes
create
more
drug
delivery
(oral
administration
ciprofloxacin,
parenteral
etoposide).
Thus,
liposomes
were
prepared
using
thin-film
hydration
technique
characterised
through
ATR-FTIR,
Dynamic
Light
Scattering
(DLS),
zeta
potential,
release
profiling.
In
both
cases,
application
enhanced
in
size
surface
charge.
Chitosome-encapsulated
formulations
exhibited
slower
sustained
profile,
while
combined
effect
chitosan
showed
heightened
efficacy
against
glioblastoma
cell
line
U373.
Therefore,
coating
improved
system's
properties,
resulting
promising
method
delivery.
Язык: Английский
Current Research Trends in Glioblastoma: Focus on Receptor Tyrosine Kinases
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(8), С. 3503 - 3503
Опубликована: Апрель 9, 2025
Glioblastoma
(GBM)
is
an
aggressive
brain
tumor
characterized
by
molecular
complexity
and
resistance
to
conventional
treatments,
including
surgery,
radiation,
chemotherapy.
Despite
these
challenges,
advancements
in
receptor
tyrosine
kinase
(RTK)
research,
combined
with
multi-omics
approaches,
hold
promise
for
improving
patient
outcomes
survivability.
RTKs
are
central
GBM
progression,
influencing
cell
proliferation,
survival,
angiogenesis.
However,
the
of
RTK
signaling
necessitates
a
broader,
integrative
perspective,
which
has
been
enabled
emergence
-omics
sciences.
Multi-omics
technologies—including
genomics,
transcriptomics,
proteomics,
metabolomics—offer
unprecedented
insights
into
landscape
its
RTK-driven
pathways.
Genomic
studies
have
revealed
mutations
amplifications
RTK-related
genes,
while
transcriptomics
uncovered
alterations
gene
expression
patterns,
providing
clearer
picture
how
aberrations
drive
behavior.
Proteomics
further
delineated
changes
protein
post-translational
modifications
linked
signaling,
highlighting
novel
therapeutic
targets.
Metabolomics
complements
findings
identifying
RTK-associated
metabolic
reprogramming,
such
as
shifts
glycolysis
lipid
metabolism,
sustain
growth
therapy
resistance.
The
integration
layers
enables
comprehensive
understanding
biology
GBM.
For
example,
activity,
offering
new
biomarkers
classification
targeting.
Additionally,
single-cell
unveiled
intratumoral
heterogeneity,
critical
factor
This
article
highlights
transformative
potential
unraveling
By
combining
researchers
paving
way
precision
medicine
strategies
that
may
significantly
enhance
diagnostic
accuracy
treatment
efficacy,
hope
patients
facing
this
devastating
disease.
Язык: Английский
A Synopsis of Biomarkers in Glioblastoma: Past and Present
Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
46(7), С. 6903 - 6939
Опубликована: Июль 3, 2024
Accounting
for
48%
of
malignant
brain
tumors
in
adults,
glioblastoma
has
been
great
interest
the
last
decades,
especially
biomolecular
and
neurosurgical
fields,
due
to
its
incurable
nature
notable
neurological
morbidity.
The
major
advancements
technologies
have
positively
influenced
extent
safe
tumoral
resection,
while
latest
progress
field
GBM
uncovered
new
potential
therapeutical
targets.
Although
currently
no
curative
therapy,
recent
made
management
this
disease,
both
from
surgical
molecular
perspectives.
main
current
therapeutic
approach
is
multimodal
consists
intervention,
radiotherapy,
chemotherapy,
mostly
with
temozolomide.
most
patients
will
develop
treatment
resistance
tumor
recurrence
after
removal,
regarding
contributed
a
better
understanding
pathology
management.
Over
past
few
specific
biomarkers
discovered
that
helped
predict
prognosis
responses
improvements
survival
rates.
Язык: Английский
The MET Oncogene: An Update on Targeting Strategies
Pharmaceuticals,
Год журнала:
2024,
Номер
17(11), С. 1473 - 1473
Опубликована: Ноя. 2, 2024
The
MET
receptor,
commonly
known
as
HGF
(hepatocyte
growth
factor)
is
a
focus
of
extensive
scientific
research.
has
been
linked
to
embryonic
development,
tissue
regeneration
following
injury,
tumorigenesis,
and
cancer
metastasis.
These
functions
underscore
its
involvement
in
numerous
cellular
processes,
including
stemness,
proliferation,
motility,
cell
dissociation,
survival.
However,
the
enigmatic
nature
becomes
apparent
context
cancer.
When
remains
persistently
activated,
since
gene
undergoes
genetic
alterations,
it
initiates
complex
signaling
cascade
setting
motion
an
aggressive
metastatic
program
that
characteristic
malignant
cells
“invasive
growth”.
expanding
knowledge
opened
up
opportunities
for
therapeutic
interventions,
particularly
realm
oncology.
Targeting
presents
promising
strategy
developing
novel
anti-cancer
treatments.
In
this
review,
we
provide
updated
overview
drugs
designed
modulate
signaling,
highlighting
kinase
inhibitors,
degraders,
anti-MET/HGF
monoclonal
antibodies,
MET-targeted
antibody–drug
conjugates.
Through
aim
contribute
ongoing
advancement
strategies
targeting
signaling.
Язык: Английский
The MET Oncogene: Thirty Years of Insights into Molecular Mechanisms Driving Malignancy
Pharmaceuticals,
Год журнала:
2024,
Номер
17(4), С. 448 - 448
Опубликована: Март 30, 2024
The
discovery
and
subsequent
research
on
the
MET
oncogene’s
role
in
cancer
onset
progression
have
illuminated
crucial
insights
into
molecular
mechanisms
driving
malignancy.
identification
of
as
hepatocyte
growth
factor
(HGF)
receptor
has
paved
path
for
characterizing
tyrosine
kinase
activation
mechanism
its
downstream
signaling
cascade.
Over
past
thirty
years,
established
importance
HGF/MET
normal
cellular
processes,
such
cell
dissociation,
migration,
proliferation,
survival.
Notably,
genetic
alterations
that
lead
to
continuous
MET,
known
constitutive
activation,
been
identified
oncogenic
drivers
various
cancers.
lesions
affecting
exon
skipping,
gene
amplification,
rearrangements,
provide
valuable
targets
therapeutic
intervention.
Moreover,
implications
a
resistance
targeted
therapies
emphasize
need
combination
treatments
include
inhibitors.
intriguing
“flare
effect”
phenomenon,
wherein
inhibition
can
post-treatment
increases
underscores
dynamic
nature
therapeutics.
In
human
tumors,
increased
protein
expression
often
occurs
without
amplification.
Various
may
cause
an
overexpression:
transcriptional
upregulation
induced
by
other
oncogenes;
environmental
factors
(such
hypoxia
or
radiation);
substances
produced
reactive
stroma,
inflammatory
cytokines,
pro-angiogenic
factors,
even
HGF
itself.
conclusion,
journey
understanding
MET’s
involvement
over
three
decades
not
only
deepened
our
knowledge,
but
also
way
innovative
strategies.
Selective
pharmacological
inactivation
stands
promising
avenue
achieving
remission,
particularly
cases
where
are
primary
Язык: Английский
Pericytes orchestrate a tumor-restraining microenvironment in glioblastoma
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 27, 2024
Abstract
Glioblastoma
(GBM)
is
characterized
by
fast
progression,
an
infiltrative
growth
pattern,
and
a
high
rate
of
relapse.
A
defining
feature
GBM
the
existence
spatially
functionally
distinct
cellular
niches,
i.e.
hypoxic
niche,
leading-edge
perivascular
in
which
malignant
cells
engage
paracrine
crosstalk
with
cell
types
comprising
tumor
microenvironment.
Here,
analysis
single-cell
transcriptomic
data
human
transgenic
mouse
models
GBM,
we
unexpectedly
identified
pericytes,
mural
intimately
associated
endothelium,
as
most
active
signaling
hub
within
parenchyma.
Exclusive
axes
emanating
from
pericytes
were
received
endothelial
cells,
astrocytes,
immune
cells.
Depletion
through
genetic
engineering
several
different
orthotopic
demonstrated
accelerated
disrupted
blood-brain-barrier,
premature
death
pericyte-poor
mice.
Mechanistic
studies
revealed
that
pericyte
deficiency
altered
composition
remodeled
impacted
on
landscape,
exacerbating
invasion
suppression.
Specifically,
deprived
association
their
programs,
turn
attracted
perivascular,
tumor-associated
macrophages
polarized
towards
immune-suppressive
phenotype.
The
recruited
expressed
Hepatocyte
Growth
Factor
(HGF),
reinforced
activation
its
receptor
tyrosine
kinase
MET
harboring
extreme
mesenchymal
subtype
driven
key
phenotypic
regulator
Fosl1
regions.
Indeed,
implantation
isolated,
MET-expressing
corroborated
superior
tumor-initiating
capability
invasive
In
patients,
low
expression
core
gene
signature
was
reduced
recurrent
compared
to
primary
tumors.
Consistently,
signatures
for
transcriptional
programs
+
Met
indicative
poor
survival
tumors,
spatial
transcriptomics
capacity.
Taken
together,
infer
represents
critical
modulator
development
orchestrating
tumor-suppressive
microenvironment;
our
findings
thus
highlight
importance
preservation
face
current
future
therapies.
Figure
Язык: Английский
Evolution of Molecular Biomarkers and Precision Molecular Therapeutic Strategies in Glioblastoma
Cancers,
Год журнала:
2024,
Номер
16(21), С. 3635 - 3635
Опубликована: Окт. 29, 2024
Glioblastoma
is
the
most
commonly
occurring
malignant
brain
tumor,
with
a
high
mortality
rate
despite
current
treatments.
Its
classification
has
evolved
over
years
to
include
not
only
histopathological
features
but
also
molecular
findings.
Given
heterogeneity
of
glioblastoma,
biomarkers
for
diagnosis
have
become
essential
initiating
treatment
therapies,
while
new
technologies
detecting
specific
variations
using
computational
tools
are
being
rapidly
developed.
Advances
in
genetics
made
possible
creation
tailored
therapies
based
on
targets,
various
degrees
success.
This
review
provides
an
overview
latest
advances
fields
histopathology
and
radiogenomics
use
markers
management
as
well
development
targeting
common
markers.
Furthermore,
we
offer
summary
results
recent
preclinical
clinical
trials
recognize
trends
investigation
understand
future
directions
targeted
glioblastoma.
Язык: Английский