Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy
Karadeniz Fen Bilimleri Dergisi,
Год журнала:
2025,
Номер
15(1), С. 519 - 535
Опубликована: Март 15, 2025
Colorectal
cancer
(CRC)
remains
a
major
global
health
challenge,
with
limited
treatment
options
for
advanced-stage
patients.
While
genomic
and
transcriptomic
analyses
aid
in
target
identification,
proteomic
alterations
offer
more
direct
link
to
tumor
biology
therapeutic
opportunities.
In
this
study,
we
analyzed
mass
spectrometry-based
proteomics
data
from
102
primary
CRC
patients,
including
matched
normal
tissues,
systematically
identify
overexpressed,
druggable
targets,
particular
focus
on
the
patient
kinome.
Using
OPPTI
approach,
discovered
31
kinases
notable
overexpression,
16
currently
targetable
by
existing
drugs,
such
as
FGR,
EPHA2,
PBK.
Furthermore,
revealed
884
overexpressed
non-kinase
proteins,
253
of
which
are
druggable,
ERAP2,
FLG,
MT1H.
Differential
expression
analysis
identified
165
dysregulated
3,903
MET
STK3
emerging
potential
candidates
due
their
substantial
upregulation.
Integrating
differential
overexpression
analyses,
highlighted
cohort
EPHA2
MET,
whose
inhibition
has
shown
promising
preclinical
efficacy.
This
comprehensive
study
provides
resource
novel
discovery
CRC,
offering
framework
personalized
interventions
through
identification
clinically
actionable
protein-level
alterations.
Язык: Английский
The MET Oncogene Network of Interacting Cell Surface Proteins
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(24), С. 13692 - 13692
Опубликована: Дек. 21, 2024
The
MET
oncogene,
encoding
the
hepatocyte
growth
factor
(HGF)
receptor,
plays
a
key
role
in
tumorigenesis,
invasion,
and
resistance
to
therapy,
yet
its
full
biological
functions
activation
mechanisms
remain
incompletely
understood.
A
feature
of
is
extensive
interaction
network,
encompassing
following:
(i)
receptor
tyrosine
kinases
(RTKs);
(ii)
co-receptors
(e.g.,
CDCP1,
Neuropilin1);
(iii)
adhesion
molecules
integrins,
tetraspanins);
(iv)
proteases
ADAM10);
(v)
other
receptors
CD44,
plexins,
GPCRs,
NMDAR).
These
interactions
dynamically
modulate
MET’s
activation,
signaling,
intracellular
trafficking,
degradation,
enhancing
functional
versatility
oncogenic
potential.
This
review
offers
current
knowledge
on
partnerships,
focusing
their
impact
signaling
output,
therapeutic
resistance,
cellular
behavior.
Finally,
we
evaluate
emerging
combination
therapies
targeting
interactors,
highlighting
potential
overcome
improve
clinical
outcomes.
By
exploring
complex
interplay
within
network
interacting
cell
surface
proteins,
this
provides
insights
into
advancing
anti-cancer
strategies
understanding
broader
implications
RTK
crosstalk
oncology.
Язык: Английский