Genes,
Год журнала:
2024,
Номер
15(4), С. 501 - 501
Опубликована: Апрель 17, 2024
Glioblastoma,
the
most
aggressive
and
common
malignant
primary
brain
tumour,
is
characterized
by
infiltrative
growth,
abundant
vascularization,
clinical
evolution.
Patients
with
glioblastoma
often
face
poor
prognoses,
a
median
survival
of
approximately
15
months.
Technological
progress
subsequent
improvement
in
understanding
pathophysiology
these
tumours
have
not
translated
into
significant
achievements
therapies
or
outcomes
for
patients.
Progress
molecular
profiling
has
yielded
new
omics
data
more
refined
classification
glioblastoma.
Several
typical
genetic
epigenetic
alterations
include
mutations
genes
regulating
receptor
tyrosine
kinase
(RTK)/rat
sarcoma
(RAS)/phosphoinositide
3-kinase
(PI3K),
p53,
retinoblastoma
protein
(RB)
signalling,
as
well
mutation
isocitrate
dehydrogenase
(IDH),
methylation
O6-methylguanine-DNA
methyltransferase
(MGMT),
amplification
epidermal
growth
factor
vIII,
codeletion
1p/19q.
Certain
microRNAs,
such
miR-10b
miR-21,
also
been
identified
prognostic
biomarkers.
Effective
treatment
options
are
limited.
Surgery,
radiotherapy,
alkylating
agent
chemotherapy
remain
pillars
treatment.
Only
promoter
gene
MGMT
predicts
benefit
from
temozolomide
it
guides
choice
first-line
elderly
targeted
strategies
based
on
tumour-intrinsic
dominant
signalling
pathways
antigenic
tumour
profiles
under
investigation
trials.
This
review
explores
potential
biomarkers
that
could
be
deployed
analytical
tools
diagnosis
prognostication
Recent
advancements
treating
discussed,
along
liquid
biopsies
to
advance
personalized
medicine
field
glioblastoma,
highlighting
challenges
promises
future.
Pharmaceutics,
Год журнала:
2024,
Номер
16(1), С. 100 - 100
Опубликована: Янв. 11, 2024
Glioblastoma
multiforme
(GBM)
is
the
most
common
type
of
glioma,
with
a
median
survival
14.6
months
post-diagnosis.
Understanding
molecular
profile
such
tumors
allowed
development
specific
targeted
therapies
toward
GBM,
major
role
attributed
to
tyrosine
kinase
receptor
inhibitors
and
immune
checkpoint
inhibitors.
Targeted
therapeutics
are
drugs
that
work
by
binding
GBM-specific
or
overexpressed
markers
on
tumor
cellular
surface
therefore
contain
recognition
moiety
linked
cytotoxic
agent,
which
produces
an
antiproliferative
effect.
In
this
review,
we
have
summarized
available
information
used
in
clinical
trials
GBM
current
obstacles
advances
therapy
concerning
targets
present
cells,
outlined
efficacy
endpoints
for
classes
investigational
drugs,
discussed
promising
strategies
towards
increase
drug
GBM.
npj Precision Oncology,
Год журнала:
2024,
Номер
8(1)
Опубликована: Фев. 20, 2024
Abstract
Glioblastoma
is
one
of
the
most
lethal
cancers
with
current
therapeutic
options
lacking
major
successes.
This
underlines
necessity
to
understand
glioblastoma
biology
on
other
levels
and
use
these
learnings
for
development
new
concepts.
Mounting
evidence
in
field
circadian
medicine
points
a
tight
interplay
between
disturbances
system
progression.
The
clock,
an
internal
biological
mechanism
governing
numerous
physiological
processes
across
24-h
cycle,
also
plays
pivotal
role
regulationg
key
cellular
functions,
including
DNA
repair,
cell
cycle
progression,
apoptosis.
These
are
integral
tumour
response
therapy.
Disruptions
rhythms
can
influence
growth,
invasion,
treatment
patients.
In
this
review,
we
explore
robust
association
cancer
hallmarks
within
context
glioblastoma.
We
further
discuss
impact
clock
eight
shown
previously
link
molecular
different
cancers,
summarize
putative
proteins
rhythm
chronotherapy
By
unravelling
mechanisms
behind
intricate
connections
researchers
pave
way
identification
potential
targets,
innovative
strategies
personalized
approaches.
conclusion,
review
underscores
significant
advancement
understanding
future
therapies
glioblastoma,
ultimately
leading
enhanced
outcomes
It
is
well
known
how
the
precise
localization
of
glioblastoma
multiforme
(GBM)
predicts
direction
tumor
spread
in
surrounding
neuronal
structures.
The
aim
present
review
to
reveal
lateralization
GBM
by
evaluating
anatomical
regions
where
it
frequently
located
as
main
molecular
alterations
observed
different
brain
regions.
According
literature,
or
most
frequent
has
yet
be
determined.
However,
can
said
that
more
frontal
lobe.
Tractus
and
fascicles
involved
appear
focused
on
corticospinal
tract,
superior
longitudinal
I,
II
III
fascicles,
arcuate
fascicle
long
segment,
strait
inferior
fronto‑occipital
fasciculus.
Considering
features
its
involvement,
logical
are
frontal‑temporal‑parietal‑occipital
lobes,
respectively.
Although
volumes
higher
right
hemisphere,
been
determined
prognosis
patients
diagnosed
with
cancer
left
hemisphere
worse,
probably
reflecting
distribution
some
detrimental
such
TP53
mutations,
PTEN
loss,
EGFR
amplification,
MGMT
promoter
methylation.
There
theories
stating
less
exposed
external
influences
development
responsible
for
functions
necessary
survival
while
tumors
may
aggressive.
To
shed
light
specific
regions,
article
aimed
at
describing
pathways
gene
mutations
epigenetic
modifications
associated
tumors.
Expert Opinion on Therapeutic Patents,
Год журнала:
2023,
Номер
33(4), С. 309 - 322
Опубликована: Апрель 3, 2023
ABSTRACTIntroduction
The
dysregulation
of
CDK9
protein
is
greatly
related
to
the
proliferation
and
differentiation
various
cancers
due
its
key
role
in
regulation
RNA
transcription.
Moreover,
inhibition
can
markedly
downregulate
anti-apoptotic
Mcl-1
which
essential
for
survival
tumors.
Thus,
targeting
considered
be
a
promising
strategy
antitumor
drug
development,
development
selective
inhibitors
has
gained
increasing
attention.Areas
covered
This
review
focuses
on
reported
patent
publications
during
period
2020–2022,
were
searched
from
SciFinder
Cortellis
Drug
Discovery
Intelligence.Expert
opinion
Given
that
pan-CDK9
may
lead
serious
side
effects
poor
selectivity,
investigation
attracted
widespread
attention.
make
some
advance
treating
solid
tumors
possess
therapeutic
potential
EGFR-mutant
lung
cancer.
with
short
half-life
intravenous
administration
might
result
transient
target
engagement
contribute
better
safety
profile
vivo.
However,
more
efforts
are
urgently
needed
accelerate
inhibitors,
including
research
new
binding
modes
between
ligand
receptor
or
sites.KEYWORDS:
CancerCDK9inhibitorsMcl-1transient
Article
highlights
strongly
associated
cancers,
hematologic
tumors.CDK9
regulate
directly
levels
own
overcome
resistance
treatment
NSCLC.Patents
regarding
(2020-2022)
collected
discussed.CDK9
also
achieve
potent
activity
vivo,
extensive
attention
researchers.More
still
vitally
perform
mechanistic
inhibitors.Declaration
interestThe
authors
have
no
relevant
affiliations
financial
involvement
any
organization
entity
interest
conflict
subject
matter
materials
discussed
manuscript.
includes
employment,
consultancies,
honoraria,
stock
ownership
options,
expert
testimony,
grants
patents
received
pending,
royaltiesReviewer
disclosuresPeer
reviewers
this
manuscript
other
relationships
disclose.Author
contributions
statementT
Wu,
X
Y
Xu
responsible
writing
whole
Z
Li
J
Bian
charge
checking
revision.
R
Chen
Wang
much
work
figures.Additional
informationFundingThis
paper
was
funded
by
National
Natural
Science
Foundation
China
(no.
81872746,
81703347
82104030),
Jiangsu
Province
BK20170743,
BK20171393
BK20210422),
State
Key
Laboratory
Research
(SIMM1903KF-03),
Postgraduate
&
Practice
Innovation
Program
(KYCX18
0770).
Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
46(12), С. 14324 - 14350
Опубликована: Дек. 19, 2024
Glioblastoma
multiforme
(GBM)
is
one
of
the
most
aggressive
and
difficult-to-treat
brain
tumors,
with
a
poor
prognosis
due
to
its
high
resistance
conventional
therapies.
Current
treatment
options,
including
surgical
resection,
radiotherapy,
chemotherapy,
have
limited
effectiveness
in
improving
long-term
survival.
Despite
emergence
new
therapies,
monotherapy
approaches
not
shown
significant
improvements,
highlighting
need
for
innovative
therapeutic
strategies.
Combination
therapies
appear
be
promising
solution,
as
they
target
multiple
molecular
pathways
involved
GBM
progression.
One
area
growing
interest
incorporation
phytotherapy
micotherapy
complementary
treatments,
which
offer
potential
benefits
their
anti-tumor,
anti-inflammatory,
immunomodulatory
properties.
This
review
examines
current
challenges
treatment,
discusses
combination
highlights
role
integrative
options
management.
Molecular Pharmaceutics,
Год журнала:
2023,
Номер
20(10), С. 4994 - 5005
Опубликована: Сен. 21, 2023
Rhizochalinin
(Rhiz)
is
a
recently
discovered
cytotoxic
sphingolipid
synthesized
from
the
marine
natural
compound
rhizochalin.
Previously,
Rhiz
demonstrated
high
in
vitro
and
vivo
efficacy
various
cancer
models.
Here,
we
report
to
be
highly
active
human
glioblastoma
cell
lines
as
well
patient-derived
glioma-stem
like
neurosphere
counteracted
proliferation
by
inducing
apoptosis,
G2/M-phase
cycle
arrest,
inhibition
of
autophagy.
Proteomic
profiling
followed
bioinformatic
analysis
suggested
suppression
Akt
pathway
one
major
biological
effects
Rhiz.
Suppression
IGF-1R
MEK1/2
kinase
was
confirmed
Rhiz-treated
GBM
cells.
In
addition,
pretreatment
resulted
more
pronounced
inhibitory
effect
γ-irradiation
on
growth
glioma-spheres,
an
which
may
also
contribute
decisively.
contrast,
EGFR
upregulation,
observed
all
neurospheres
under
treatment,
postulated
possible
sign
incipient
resistance.
line
with
this,
combinational
therapy
EGFR-targeted
tyrosine
inhibitors
synergistically
increased
resulting
dramatic
viability
significant
reduction
size
case
combination
lapatinib.
Preliminary
data
generated
using
parallel
artificial
membrane
permeability
(PAMPA)
assay
that
cannot
cross
blood
brain
barrier
therefore
alternative
drug
delivery
methods
should
used
further
studies.
conclusion,
promising
new
candidate
for
treatment
glioblastoma,
developed
inhibitors.
Biomedicines,
Год журнала:
2023,
Номер
11(12), С. 3168 - 3168
Опубликована: Ноя. 28, 2023
Glioblastoma
(GBM)
is
a
representative
malignant
brain
tumor
characterized
by
dismal
prognosis,
with
survival
rates
of
less
than
2
years
and
high
recurrence
rates.
Despite
surgical
resection
several
alternative
treatments,
GBM
remains
refractory
disease
due
to
its
aggressive
invasiveness
resistance
anticancer
therapy.
In
this
report,
we
explore
the
role
fibronectin
type
III
domain
containing
3B
(FNDC3B)
potential
as
prognostic
therapeutic
biomarker
in
GBM.
exhibited
significantly
higher
cancer-to-normal
ratio
compared
other
organs,
patients
FNDC3B
expression
had
poor
prognosis
(p
<
0.01).
vitro
studies
revealed
that
silencing
reduced
Survivin,
an
apoptosis
inhibitor,
also
cell
migration,
invasion,
extracellular
matrix
adhesion
ability,
stem
properties
cells.
Furthermore,
identified
regulates
PTEN/PI3K/Akt
signaling
cells
using
MetaCore
integrated
pathway
bioinformatics
analysis
proteome
profiler
phospho-kinase
array
sequential
western
blot
analysis.
Collectively,
our
findings
suggest
for
predicting
patient
development
treatment
strategies
