Abstract
Tumor
progression
depends
on
angiogenesis,
which
is
stimulated
by
growth
factors
like
VEGF,
targeting
VEGFR
kinase
with
small
molecules
an
effective
anti‐angiogenic
therapeutic
approach.
The
rational
modification
of
sunitinib
(VEGFR‐2
inhibitor)
to
spirocyclopropyloxindoline
carboxamides
have
been
performed
and
their
in
vitro
cytotoxic
profiling
was
evaluated.
molecular
modelling
studies
enabled
the
screening
designed
analogues
identifying
possible
interactions
within
type
III
allosteric
inhibitor
binding
site
VEGFR‐2.
biological
synthesized
compounds
15
a
–
y
,
revealed
ability
compound
w
inhibit
cell
MCF‐7
line
IC
50
value
3.87±0.19
μM
alongside
inhibition
VEGFR‐2
at
concentration
4.34±0.13
observed.
Also,
validated
through
HUVEC
tube
formation
assay.
qualitative
assessment
apoptosis
induction
cells
evaluated
staining
such
as
AO/EB
DAPI
staining,
whereas
quantification
cycle
analysis
were
FACS
analysis.
metastatic
cancer
migration
scratch
wound
healing
current
study
strives
sequentially
optimize
structural
attributes
3‐alkenyl
oxindole
core
surpass
existing
challenges
well‐known
inhibitors.
findings
observed
from
this
highlights
that
be
prominent
lead
towards
development
clinical
drug
candidates.
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.
Molecular Aspects of Medicine,
Год журнала:
2025,
Номер
101, С. 101335 - 101335
Опубликована: Янв. 1, 2025
Renal
cell
carcinoma
(RCC)
is
a
malignant
tumor
with
highly
heterogeneous
and
complex
molecular
mechanisms.
Through
systematic
analysis
of
TCGA,
COSMIC
other
databases,
24
mutated
genes
closely
related
to
RCC
were
screened,
including
VHL,
PBRM1,
BAP1
SETD2,
which
play
key
roles
in
signaling
pathway
transduction,
chromatin
remodeling
DNA
repair.
The
PI3K/AKT/mTOR
particularly
important
the
pathogenesis
RCC.
Mutations
such
as
PIK3CA,
MTOR
PTEN
are
associated
metabolic
abnormalities
proliferation.
Clinically,
mTOR
inhibitors
VEGF-targeted
drugs
have
shown
significant
efficacy
personalized
therapy.
Abnormal
regulation
reprogramming,
especially
glycolysis
glutamine
pathways,
provides
cells
continuous
energy
supply
survival
advantages,
GLS1
promising
results
preclinical
studies.
This
paper
also
explores
potential
immune
checkpoint
combination
targeted
drugs,
well
application
nanotechnology
drug
delivery
In
addition,
unique
mechanisms
revealed
individualized
therapeutic
strategies
explored
for
specific
subtypes
TFE3,
TFEB
rearrangement
type
SDHB
mutant
type.
review
summarizes
common
gene
mutations
their
mechanisms,
emphasizes
diagnosis,
treatment
prognosis,
looks
forward
prospects
multi-pathway
therapy,
immunotherapy
treatment,
providing
theoretical
support
clinical
guidance
new
development.
Journal of Cellular and Molecular Medicine,
Год журнала:
2025,
Номер
29(1)
Опубликована: Янв. 1, 2025
The
development
of
efficient
platforms
for
the
evaluation
anti-angiogenic
agents
is
critical
in
advancing
cancer
therapeutics.
In
this
study,
we
exploited
an
ultrabright
semiconducting
polymer
dots
(Pdots)
integrating
with
a
three-dimensional
(3D)
near-infrared-II
(NIR-II)
fluorescence
imaging
system
designed
to
assess
efficacy
potent
PX-478
and
BPR0C261
oral
squamous
cell
carcinoma
(OSCC)
tumour
model,
which
depends
on
angiogenesis
dissemination.
PX-478,
hypoxia-inducible
factor-1α
(HIF-1α)
inhibitor,
BPR0C261,
microtubule-disrupting
agent,
were
administrated
into
tumour-bearing
mice
established
using
murine
MTCQ1
tongue
cells
through
intraperitoneal
injection
gavage,
respectively.
Our
findings
showed
that
significantly
inhibited
growth
extended
life
span
without
decreasing
body
weights.
Pdots-based
NIR-II
vascular
demonstrated
vascularity
was
suppressed
by
BPRC0261.
Accordingly,
excised
tumours
treated
less
blood
vessels
than
vehicles.
expression
endothelial
markers
CD31
also
found
be
reduced
BPRC0261
immunohistochemical
(IHC)
staining
Western
blot
analysis.
Furthermore,
could
suppress
HIF-1α
factor-A
(VEGF-A),
but
only
VEGF-A.
Taken
together,
innovative
3D
combining
biocompatible
Pdots
unique
optical
specificity
enables
non-invasive,
real-time
monitoring
compounds.
Biomaterials Research,
Год журнала:
2025,
Номер
29
Опубликована: Янв. 1, 2025
Tumors
grow
by
receiving
oxygen
and
nutrients
from
the
surrounding
blood
vessels,
leading
to
rapid
angiogenesis.
This
results
in
functionally
structurally
abnormal
vasculature
characterized
high
permeability
irregular
flow,
causing
hypoxia
within
tumor
microenvironment
(TME).
Hypoxia
exacerbates
secretion
of
pro-angiogenic
factors
such
as
vascular
endothelial
growth
factor
(VEGF),
further
perpetuating
vessel
formation.
environment
compromises
efficacy
radiotherapy,
immunotherapy,
chemotherapy.
In
this
study,
we
developed
a
pH-sensitive
liposome
(PSL)
system,
termed
OD_PSL@AKB,
co-deliver
(OD)
razuprotafib
(AKB-9778)
tumors.
system
rapidly
responds
acidic
TME
alleviate
inhibit
VEGF
secretion,
restoring
VE-cadherin
expression
hypoxic
cell/cancer
cell
cocultures.
Our
findings
highlight
potential
OD_PSL@AKB
normalizing
improving
therapeutic
efficacy.
Pharmaceuticals,
Год журнала:
2025,
Номер
18(2), С. 280 - 280
Опубликована: Фев. 19, 2025
Colorectal
cancer
(CRC)
is
one
of
the
most
common
malignancies
worldwide,
with
high
morbidity
and
mortality
rates.
Conventional
treatments,
including
surgery,
radiotherapy,
chemotherapy,
have
limited
effects
on
advanced
metastatic
CRC
(mCRC).
Fruquintinib,
a
novel
highly
selective
vascular
endothelial
growth
factor
receptor
(VEGFR)
inhibitor,
has
shown
significant
efficacy
tolerance
in
treating
mCRC.
The
FRESCO
FRESCO-2
trials
demonstrated
that
fruquintinib
significantly
prolongs
progression-free
survival
overall
refractory
mCRC
patients,
establishing
it
as
standard
third-line
treatment
strategy
for
In
addition,
combination
other
anticancer
drugs
immune
checkpoint
inhibitors
potential
enhanced
efficacy,
which
warrants
further
exploration.
this
review,
we
aimed
to
systematically
summarize
current
knowledge
about
pharmacological
mechanisms,
pharmacokinetic
characteristics,
adverse
events,
corresponding
options
provide
an
update
clinical
related
by
conducting
comprehensive
literature
search
PubMed
consulting
relevant
via
ClinicalTrials.gov
ChiCTR
website,
aiming
offer
new
insights
into
role
CRC.
