Drug Development Research,
Год журнала:
2024,
Номер
86(1)
Опубликована: Дек. 25, 2024
ABSTRACT
The
remarkable
clinical
success
of
third‐generation
epidermal
growth
factor
receptor‐tyrosine
kinase
inhibitors
(EGFR‐TKIs)
has
significantly
advanced
the
treatment
landscape
for
non‐small‐cell
lung
cancer
(NSCLC).
However,
emergence
tertiary
point
mutation
C797S
poses
a
substantial
obstacle
to
their
efficacy,
leading
dearth
FDA‐approved
targeted
therapies
patients
harboring
this
mutation.
Addressing
pressing
challenge
necessitates
development
novel
therapeutic
agents
targeting
clinically
challenging
EGFR
This
review
delves
into
design
strategies,
antitumor
activity,
and
crucial
protein–drug
interactions
recently
introduced
Orthoallosteric
fourth‐generation
EGFR‐TKIs.
These
are
distinguished
by
ability
simultaneously
engage
both
canonical
orthosteric
(ATP)
binding
site
allosteric
site.
By
shedding
light
on
these
key
aspects,
serves
as
valuable
resource
medicinal
chemists,
empowering
them
propel
advancement
inhibitors.
Cancer Drug Resistance,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 14, 2025
Aim:
Lung
adenocarcinoma
(LUAD),
the
most
prevalent
subtype
of
non-small
cell
lung
cancer
(NSCLC),
presents
significant
clinical
challenges
due
to
its
high
mortality
and
limited
therapeutic
options.
The
molecular
heterogeneity
development
resistance
further
complicate
treatment,
underscoring
need
for
a
more
comprehensive
understanding
cellular
characteristics.
This
study
sought
delineate
novel
subpopulations
subtypes
LUAD,
identify
critical
biomarkers,
explore
potential
targets
enhance
treatment
efficacy
patient
prognosis.
Methods:
An
integrative
multi-omics
approach
was
employed
incorporate
single-cell
RNA
sequencing
(scRNA-seq),
bulk
transcriptomic
analysis,
genome-wide
association
(GWAS)
data
from
multiple
LUAD
cohorts.
Advanced
computational
approaches,
including
Bayesian
deconvolution
machine
learning
algorithms,
were
used
comprehensively
characterize
tumor
microenvironment,
classify
subtypes,
develop
robust
prognostic
model.
Results:
Our
analysis
identified
eleven
distinct
within
with
epithelial
cells
predominating
exhibiting
mutation
frequencies
in
Tumor
Protein
53
(TP53)
Titin
(TTN)
genes.
Two
[consensus
(CS)1
CS2]
identified,
each
showing
immune
landscapes
outcomes.
CS2
subtype,
characterized
by
increased
infiltration,
demonstrated
favorable
prognosis
higher
sensitivity
immunotherapy.
Furthermore,
multi-omics-driven
signature
(MOMLS)
ribonucleotide
reductase
M1
(RRM1)
as
biomarker
associated
chemotherapy
response.
Based
on
this
model,
several
agents
targeting
different
proposed.
Conclusion:
framework
complexity
providing
insights
into
heterogeneity,
targets.
Differential
immunotherapy
among
various
paving
way
future
immunotherapy-focused
research.
PeerJ,
Год журнала:
2025,
Номер
13, С. e19135 - e19135
Опубликована: Март 26, 2025
Novel
treatment
techniques
are
needed
since
lung
cancer
is
still
a
major
worldwide
health
concern.
Green
tea
contains
component
called
epigallocatechin-3-gallate
(EGCG),
which
has
demonstrated
potential
anticancer
properties.
This
work
sought
to
understand
how
EGCG
affects
the
phosphatidylinositol-3-kinase
protein
kinase
B
(PI3K/Akt)
signaling
pathway,
in
turn
causes
apoptosis
H1299
cells.
In
this
experiment,
multiple
dosages
of
were
applied
five
cells
and
A549
cell
lines
for
duration
72
h.
Apoptotic
pathways,
cellular
responses,
expression
levels
investigated
relation
by
morphological,
biochemical,
proliferation/migration
investigations.
cells,
raised
rates
and,
dose-dependent
way,
hindered
growth.
The
phosphorylated
Akt
(p-Akt)
PI3K
(p-PI3K)
dramatically
reduced
following
administration,
despite
no
significant
alterations
expressions.
These
results
imply
that
inhibits
activation
PI3K/Akt
research
provides
insights
into
effects
on
proliferation
migratory
inhibition,
as
well
highlighting
its
induce
support
EGCG's
promise
therapeutic
agent
further
our
understanding
processes
underlying
activities.
Physical Chemistry Chemical Physics,
Год журнала:
2024,
Номер
26(35), С. 22853 - 22857
Опубликована: Янв. 1, 2024
The
integration
of
SEIRA
spectroscopy
with
MD
simulation
reveals
structural
differences
in
the
compactness
and
hydration
helical
motifs
between
active
inactive
EGFR
conformations
allowing
to
study
impacts
mutations.
Cancer Drug Resistance,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 16, 2024
Primary
and
secondary
resistance
to
immune
checkpoint
blockade
(ICB)
reduces
its
efficacy.
The
mechanisms
underlying
immunotherapy
are
highly
complex.
In
non-small
cell
lung
cancer
(NSCLC),
these
primarily
associated
with
the
loss
of
programmed
death-ligand
1
(PD-L1)
expression,
genetic
mutations,
circular
RNA
axis
transcription
factor
regulation,
antigen
presentation
disorders,
dysregulation
signaling
pathways.
Additionally,
alterations
in
tumor
microenvironment
(TME)
play
a
pivotal
role
driving
resistance.
is
mainly
attributed
TME
alterations,
including
mutations
co-mutations,
modulation
T
infiltration,
enrichment
M2
tumor-associated
macrophages
(M2-TAMs)
mucosal-associated
invariant
(MAIT)
cells,
vascular
endothelial
growth
(VEGF),
pulmonary
fibrosis.
Acquired
stems
from
changes
cellular
infiltration
patterns
leading
“cold”
or
“hot”
tumors,
altered
interferon
(IFN)
pathway
involvement
extracellular
vesicles
(EVs),
oxidative
stress
responses,
as
well
post-treatment
gene
circadian
rhythm
disruption
(CRD).
This
review
presents
an
overview
various
ICB,
elucidates
during
primary,
adaptive,
acquired
resistance,
discusses
existing
strategies
for
overcoming
ICB
