MedComm – Oncology,
Journal Year:
2025,
Volume and Issue:
4(2)
Published: April 14, 2025
ABSTRACT
Osimertinib
is
the
only
third‐generation
EGFR
tyrosine
kinase
inhibitor
clinically
approved
for
first‐line
treatment
of
advanced
NSCLC
patients
harboring
mutations.
However,
drug
resistance
severely
hinders
its
clinical
efficacy.
Acquired
MET
amplification
an
important
mechanism
causing
osimertinib
resistance.
This
study
first
to
identify
fexofenadine,
originally
indicated
allergic
rhinitis
and
chronic
urticaria,
as
a
putative
Met‐inhibitor
by
in
silico
chemical‐protein
interactome
analysis
known
Met
inhibitors.
Fexofenadine
was
verified
inhibit
recombinant
cell‐free
assay
phosphorylation
other
downstream
signaling
molecules
osimertinib‐resistant
cell
lines.
KINOME
profiling
revealed
similar
inhibition
profile
between
fexofenadine
Met‐inhibiting
cabozantinib
using
Spearman
rank‐order
correlation
analysis.
Among
tested
lines,
most
efficacious
potentiating
NCI‐H820
(having
EGFR‐T790M
mutation).
Transcriptome
that
differentially
expressed
genes
following
were
enriched
epithelial‐mesenchymal
transition‐related
biological
pathways.
Importantly,
also
shown
significantly
potentiate
antitumor
effect
drug‐refractory
patient‐derived
tumor
xenograft
model
NSG
mice,
without
inducing
notable
adverse
effects.
These
findings
advocate
evaluation
repurposing
overcome
Pharmaceuticals,
Journal Year:
2024,
Volume and Issue:
17(11), P. 1473 - 1473
Published: Nov. 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.
RSC Advances,
Journal Year:
2024,
Volume and Issue:
14(41), P. 30346 - 30363
Published: Jan. 1, 2024
New
series
of
triazolo[4,3-
b
]pyridazine
derivatives
were
created.
Compounds
4a
and
4g
demonstrated
extensive
antiproliferative
activity
on
various
cell
lines.
Compound
displayed
higher
dual
inhibition
c-Met
Pim-1.
Frontiers in Chemistry,
Journal Year:
2024,
Volume and Issue:
12
Published: Dec. 10, 2024
Recently,
research
into
the
oncogenic
driver
genes
associated
with
non-small
cell
lung
cancer
(NSCLC)
has
advanced
significantly,
leading
to
development
and
clinical
application
of
an
increasing
number
approved
therapeutic
agents.
Among
these,
small
molecule
inhibitors
that
target
mesenchymal-epithelial
transition
(MET)
have
demonstrated
successful
in
settings.
Currently,
three
categories
MET
inhibitors,
characterized
by
distinct
binding
patterns
kinase
region,
been
developed:
types
Ia/Ib,
II,
III.
This
review
thoroughly
examines
MET’s
structure
its
crucial
role
NSCLC
initiation
progression,
explores
discovery
strategies
for
discusses
advancements
understanding
resistance
mechanisms.
These
insights
are
anticipated
enhance
a
new
generation
high
efficiency,
selectivity,
low
toxicity,
thereby
offering
additional
alternatives
patients
diagnosed
NSCLC.
