The
regulatory
approvals
of
tumor
agnostic
therapies
have
led
to
reevaluation
the
drug
development
process.
Conventional
models
are
histology-based.
On
other
hand,
a
new
(or
combination)
focuses
on
targeting
common
genomic
biomarker
in
multiple
cancers,
regardless
histology.
Basket-like
clinical
trials
with
cohorts
allow
clinicians
evaluate
pan-cancer
efficacy
and
toxicity.
There
currently
8
granted
by
Food
Drug
Administration
(FDA).
This
includes
two
immune
checkpoint
inhibitors,
5
targeted
therapy
agents.
Pembrolizumab
is
an
anti-PD-1
antibody
that
was
first
FDA
approved
treatment
for
unresectable
or
metastatic
microsatellite
instability-high
(MSI-H)
deficient
mismatch
repair
(dMMR)
solid
tumors
2017.
It
later
mutational
burden-high
(TMB-H)
tumors,
although
TMB
cut-off
used
still
debated.
Subsequently,
2021,
another
antibody,
Dostarlimab
also
dMMR
refractory
setting.
Patients
fusion-positive
cancers
typically
difficult
treat
due
their
rare
prevalence
distribution.
Gene
rearrangements
fusions
present
variety
tumors.
neurotrophic
tyrosine
kinase
(NTRK)
range
pediatric
adult
varying
frequency.
Larotrectinib
entrectinib
were
cancers.
Similarly,
selpercatinib
Rearranged
During
Transfection
(RET)
combination
dabrafenib,
B-Raf
Proto-Oncogene
Serine/Threonine
Kinase
(BRAF)
inhibitor,
plus
trametinib,
mitogen-activated
protein
(MEK)
inhibitor
patients
6
months
older
(except
colorectal
cancer)
carrying
BRAFV600E
mutation.
most
recent
approval
fam-trastuzumab
deruxtecan-nxki
(T-Dxd)
HER2-positive
important
identify
expeditiously
develop
drugs
potential
provide
benefit
across
types.
Abstract
Hepatocellular
carcinoma
(HCC)
is
the
most
common
primary
liver
cancer
with
a
high
mortality
rate.
It
regarded
as
significant
public
health
issue
because
of
its
complicated
pathophysiology,
metastasis,
and
recurrence
rates.
There
are
no
obvious
symptoms
in
early
stage
HCC,
which
often
leads
to
delays
diagnosis.
Traditional
treatment
methods
such
surgical
resection,
radiotherapy,
chemotherapy,
interventional
therapies
have
limited
therapeutic
effects
for
HCC
patients
or
metastasis.
With
development
molecular
biology
immunology,
signaling
pathways
immune
checkpoint
were
identified
main
mechanism
progression.
Targeting
these
molecules
has
become
new
direction
HCC.
At
present,
combination
targeted
drugs
inhibitors
first
choice
advanced
patients.
In
this
review,
we
mainly
focus
on
cutting‐edge
research
corresponding
therapy
immunotherapy
great
significance
comprehensively
understand
pathogenesis
search
potential
targets,
optimize
strategies
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(10), С. 5489 - 5489
Опубликована: Май 17, 2024
Over
120
small-molecule
kinase
inhibitors
(SMKIs)
have
been
approved
worldwide
for
treating
various
diseases,
with
nearly
70
FDA
approvals
specifically
cancer
treatment,
focusing
on
targets
like
the
epidermal
growth
factor
receptor
(EGFR)
family.
Kinase-targeted
strategies
encompass
monoclonal
antibodies
and
their
derivatives,
such
as
nanobodies
peptides,
along
innovative
approaches
use
of
degraders
protein
interaction
inhibitors,
which
recently
demonstrated
clinical
progress
potential
in
overcoming
resistance.
Nevertheless,
kinase-targeted
encounter
significant
hurdles,
including
drug
resistance,
greatly
impacts
benefits
patients,
well
concerning
toxicity
when
combined
immunotherapy,
restricts
full
utilization
current
treatment
modalities.
Despite
these
challenges,
development
remains
highly
promising.
The
extensively
studied
tyrosine
family
has
70%
its
stages
development,
while
30%
inadequately
explored.
Computational
technologies
play
a
vital
role
accelerating
novel
repurposing
existing
drugs.
Recent
FDA-approved
SMKIs
underscore
importance
blood-brain
barrier
permeability
long-term
patient
benefits.
This
review
provides
comprehensive
summary
recent
based
mechanisms
action
targets.
We
summarize
latest
developments
new
explore
emerging
inhibition
from
perspective.
Lastly,
we
outline
obstacles
future
prospects
inhibition.
Abstract
There
are
five
fibroblast
growth
factor
receptors
(FGFRs),
namely,
FGFR1–FGFR5.
When
FGFR
binds
to
its
ligand,
(FGF),
it
dimerizes
and
autophosphorylates,
thereby
activating
several
key
downstream
pathways
that
play
an
important
role
in
normal
physiology,
such
as
the
Ras/Raf/mitogen‐activated
protein
kinase
kinase/extracellular
signal‐regulated
kinase,
phosphoinositide
3‐kinase
(PI3K)/AKT,
phospholipase
C
gamma/diacylglycerol/protein
c,
signal
transducer
activator
of
transcription
pathways.
Furthermore,
oncogene,
genetic
alterations
were
found
7.1%
tumors,
these
include
gene
amplification,
mutations,
fusions
or
rearrangements.
Therefore,
rearrangements,
considered
potential
biomarkers
therapeutic
response
for
tyrosine
inhibitors
(TKIs).
However,
is
worth
noting
with
increased
use,
resistance
TKIs
inevitably
develops,
well‐known
gatekeeper
mutations.
Thus,
overcoming
development
drug
becomes
a
serious
problem.
This
review
mainly
outlines
family
functions,
related
pathways,
agents
tumors
aim
obtaining
better
outcomes
cancer
patients
changes.
The
information
provided
this
may
provide
additional
ideas
tumor
abnormalities.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 19, 2024
Fibroblast
growth
factors
(FGFs)
are
a
versatile
family
of
peptide
that
involved
in
various
biological
functions,
including
cell
and
differentiation,
embryonic
development,
angiogenesis,
metabolism.
Abnormal
FGF/FGF
receptor
(FGFR)
signaling
has
been
implicated
the
pathogenesis
multiple
diseases
such
as
cancer,
metabolic
diseases,
inflammatory
diseases.
It
is
worth
noting
macrophage
polarization,
which
involves
distinct
functional
phenotypes,
plays
crucial
role
tissue
repair,
homeostasis
maintenance,
immune
responses.
Recent
evidence
suggests
FGF/FGFR
closely
participates
polarization
macrophages,
indicating
they
could
be
potential
targets
for
therapeutic
manipulation
associated
with
dysfunctional
macrophages.
In
this
article,
we
provide
an
overview
structure,
function,
downstream
regulatory
pathways
FGFs,
well
crosstalk
between
FGF
polarization.
Additionally,
summarize
application
harnessing
to
modulate
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 4, 2025
This
study
developed
a
prognostic
model
for
patients
with
colon
adenocarcinoma
(COAD)
based
on
glycosylation-associated
genes.
By
analyzing
TCGA-COAD
data,
110
key
genes
were
identified,
and
incorporating
five
glycosylation-related
was
constructed.
The
exhibits
good
predictive
performance
is
significantly
associated
clinical
features
such
as
age,
N
stage,
M
lymph
node
count.
are
involved
in
various
biological
processes
pathways,
influence
T
cell
differentiation,
may
contribute
to
CRC
development.
High-risk
show
higher
degree
of
immune
infiltration.
aids
the
early
diagnosis,
prognosis
assessment,
treatment
planning
CRC,
offers
direction
further
research.
Abstract
Bladder
cancer
is
one
of
the
most
frequently
occurring
cancers
worldwide.
At
diagnosis,
75%
urothelial
bladder
cases
have
non-muscle
invasive
while
25%
muscle
or
metastatic
disease.
Aberrantly
activated
fibroblast
growth
factor
receptor
(FGFR)-3
has
been
implicated
in
pathogenesis
cancer.
Activating
mutations
FGFR3
are
observed
around
70%
NMIBC
and
~
15%
MIBCs.
Activated
leads
to
ligand-independent
dimerization
activation
downstream
signaling
pathways
that
promote
cell
proliferation
survival.
an
important
therapeutic
target
cancer,
clinical
studies
shown
benefit
FGFR
inhibitors
a
subset
patients.
c-MYC
well-known
major
driver
carcinogenesis
commonly
deregulated
oncogenes
identified
human
cancers.
Studies
antitumor
effects
inhibition
dependent
cells
other
may
be
mediated
through
c-MYC,
key
effector
involved
tumorigenesis.
This
review
will
summarize
current
general
understanding
MYC
alterations
role
dysregulation
with
possible
implications.
Cells,
Год журнала:
2024,
Номер
13(7), С. 571 - 571
Опубликована: Март 25, 2024
Extracellular
vesicles
(EVs)
are
secreted
from
many
tumors,
including
glioblastoma
multiforme
(GBM),
the
most
common
and
lethal
brain
tumor
in
adults,
which
shows
high
resistance
to
current
therapies
poor
patient
prognosis.
Given
relevance
of
information
provided
by
cancer
cell
secretome,
we
performed
a
proteomic
analysis
microvesicles
(MVs)
exosomes
(EXOs)
released
GBM-derived
stem
cells
(GSCs).
The
latter,
obtained
GBM
patients,
expressed
P2X7
receptors
(P2X7Rs),
positively
correlate
with
growth
invasiveness.
P2X7R
stimulation
GSCs
caused
significant
changes
EV
content,
mostly
ex
novo
inducing
or
upregulating
expression
proteins
related
cytoskeleton
reorganization,
motility/spreading,
energy
supply,
protection
against
oxidative
stress,
chromatin
remodeling,
transcriptional
regulation.
Most
induced/upregulated
have
already
been
identified
as
diagnostic/prognostic
factors,
while
others
only
reported
peripheral
tumors.
Our
findings
indicate
that
enhances
transport
and,
therefore,
possible
intercellular
exchange
aggressiveness-increasing
GSC-derived
EVs.
Thus,
P2X7Rs
could
be
considered
new
druggable
target
human
GBM,
although
these
data
need
confirmed
larger
experimental
sets.
