ACS Omega,
Journal Year:
2024,
Volume and Issue:
9(50), P. 49662 - 49673
Published: Dec. 6, 2024
RET
receptor
tyrosine
kinase
is
crucial
for
nerve
and
tissue
development
but
can
be
an
important
oncogenic
driver.
This
study
focuses
on
exploring
the
design
principles
of
potent
inhibitors
through
molecular
docking
3D-QSAR
modeling
5,6-fused
bicyclic
heteroaromatic
derivatives.
First
all,
49
different
substructures
were
collected
from
five
data
sources
selected
simulations.
QSAR
models
built
3399
conformers
952
using
partial
least-squares
method
statistically
evaluated.
The
optimal
model
exhibited
high
predictive
performance,
with
Expert Review of Clinical Pharmacology,
Journal Year:
2024,
Volume and Issue:
17(5-6), P. 477 - 487
Published: April 18, 2024
Single-arm
trials
(SATs)
and
surrogate
endpoints
were
adopted
as
pivotal
evidence
for
accelerated
approval
of
anticancer
drugs
more
than
30
years.
However,
concerns
regarding
clinical
quality
in
trials,
particularly
the
SATs
have
increasingly
been
raised.
SAT
may
not
always
provide
strong
due
to
lack
control
endpoint
overall
survival
that
is
typically
present
randomized
controlled
trials.
Clinical
trial
adjudication
a
crucial
factor
outcome
measurement
ensure
data
drugs.
In
this
review,
we
systematically
discuss
characteristics
adjudications
assessments
safety
respectively,
which
are
essential
ensuring
reliable
transparent
outcomes.
Endpoint
effectively
reduces
potential
bias
mitigates
variance
be
introduced
by
investigators
when
analyzing
medical
records
endpoints.
We
analyze
advantages
disadvantages
each
type
adjudicator
summary
roles
adjudicators.
By
suggestion
improving
reliability
transparency
review
aims
supply
strategy
better
investigation
drugs,
ultimately
leading
patient
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(13), P. 10530 - 10530
Published: June 23, 2023
RET-kinase-activating
gene
rearrangements
occur
in
approximately
1–2%
of
non-small-cell
lung
carcinomas
(NSCLCs).
Their
reliable
detection
requires
next-generation
sequencing
(NGS),
while
conventional
methods,
such
as
immunohistochemistry
(IHC),
fluorescence
situ
hybridization
(FISH)
or
variant-specific
PCR,
have
significant
limitations.
We
developed
an
assay
that
compares
the
level
RNA
transcripts
corresponding
to
5′-
and
3′-end
portions
RET
gene;
this
test
relies
on
fact
translocations
result
upregulation
kinase
domain
and,
therefore,
5′/3′-end
expression
imbalance.
The
present
study
included
16,106
consecutive
NSCLC
patients,
14,449
(89.7%)
whom
passed
cDNA
quality
control.
unbalanced
was
observed
184
(1.3%)
tumors,
169
which
had
a
sufficient
amount
material
for
identification
translocation
variants.
Variant-specific
PCR
revealed
155/169
(91.7%)
tumors.
RNA-based
NGS
10
cases,
8
carried
exceptionally
rare
novel
(HOOK1::RET
ZC3H7A::RET)
translocations.
also
applied
eight
common
4680
emerged
negative
upon
test;
33
(0.7%)
these
NSCLCs
showed
fusion.
While
combination
analysis
imbalance
allowed
2%
NSCLCs,
estimate
approached
120/2361
(5.1%)
EGFR/KRAS/ALK/ROS1/BRAF/MET-negative
carcinomas.
RET-rearranged
tumors
obtained
from
females,
but
not
males,
decreased
thymidylate
synthase
(p
<
0.00001),
is
known
predictive
marker
efficacy
pemetrexed.
results
our
provide
viable
alternative
testing
facilities
do
access
due
cost
technical
Translational Lung Cancer Research,
Journal Year:
2023,
Volume and Issue:
12(9), P. 1949 - 1958
Published: Sept. 1, 2023
The
ARROW
study
demonstrated
favorable
clinical
efficacy
and
safety
of
pralsetinib
(PRL)
in
treating
rearranged
during
transfection
(RET)
fusion
positive
non-small
cell
lung
cancer
(NSCLC)
trials.
However,
due
to
the
high
cost
PRL,
evaluating
its
cost-effective
characteristics
is
crucial.
Currently,
there
has
been
no
cost-effectiveness
analysis
specifically
for
PRL.
Therefore,
aim
this
was
assess
using
PRL
as
a
first-line
therapy
versus
reserving
it
until
second-line
solely
relying
on
chemotherapy
from
perspective
payers
United
States.A
Markov
model
developed
evaluate
3
above
mentioned
PRL-based
treatment
strategies.
Clinical
data
trial
were
incorporated
into
model,
costs
utilities
values
obtained
through
previously
published
literature
public
databases,
with
both
being
discounted
at
3%
per
year.
To
ensure
robustness
probabilistic
univariate
sensitivity
analyses
performed.
primary
endpoints
included
quality-adjusted
life
years
(QALYs),
lifetime
costs,
incremental
ratio
(ICER).Compared
chemotherapy,
use
resulted
an
additional
0.07
QALYs
$133,561,
ICER
$1,353,849.65
QALY.
Similarly,
when
used
setting,
led
0.09
$92,797,
$559,232.70
value
or
strategy
higher
than
US
willingness-to-pay
(WTP)
threshold
$150,000
Univariable
revealed
that
utility
progressed
disease
had
most
significant
impact
ICER.
be
considered
WTP
QALY,
would
need
reduced
by
71.34%
84.49%
treatment.Based
current
pricing,
neither
nor
found
patients
RET
fusion-positive
advanced
NSCLC
compared
chemotherapy.
Reserving
may
compromise
approach
maintaining
control
over
healthcare
expenses
yet
still
achieving
outcomes.
Cancer Research Statistics and Treatment,
Journal Year:
2024,
Volume and Issue:
7(1), P. 82 - 90
Published: Jan. 1, 2024
Rearranged
during
transfection
(
RET
)
alteration
promotes
oncogenesis
in
a
few
cancers.
mutation
positivity
is
seen
approximately
70%
of
medullary
thyroid
cancers,
around
30%
differentiated
papillary
and
1-2%
non-small-cell
lung
cancers
(NSCLC).
To
write
this
narrative
drug
review,
we
searched
various
websites
like
the
United
States
Food
Drug
Administration,
PubMed,
Google
Scholar,
UpToDate,
recently
published
papers
international
conferences
using
search
terms
“RET,”
“RET
alteration,”
“Retevmo,”
inhibitors,”
“selpercatinib.”
We
shortlisted
31
articles
between
January
1980
2024.
discuss
history,
mechanism
action,
resistance,
pharmacodynamics,
pharmacokinetics,
dosing,
toxicity,
pivotal
trials,
indications
selpercatinib.
Selective
inhibitors
selpercatinib
are
indicated
treatment
-altered
NSCLC
cancer.
Frontiers in Oncology,
Journal Year:
2024,
Volume and Issue:
14
Published: Dec. 24, 2024
This
study
reports
a
50-year-old
patient
presented
with
eczematous
drug-eruption
induced
by
selpercatinib
after
the
treatment
of
non-small
cell
lung
cancer
(NSCLC).
The
has
symmetric
erythematous
papules
and
plaques
all
over
body
dry,
scaly
skin
accompanied
severe
pruritus
visible
scarring.
After
systemic
glucocorticoids,
patient’
lesions
were
reduced
well.
Currently,
medical
literature
on
incidence
selpercatinib-induced
cutaneous
reactions
their
clinical
management
is
scarce.
Therefore,
this
provides
novel
evidence
for
reactions.
OncoTargets and Therapy,
Journal Year:
2023,
Volume and Issue:
Volume 16, P. 1015 - 1020
Published: Nov. 1, 2023
Objective:
Combined
small
cell
lung
cancer
(C-SCLC)
is
a
relatively
rare
subtype
of
(SCLC)
which
combines
SCLC
and
any
component
non-small
carcinoma
(NSCLC).
Patients
diagnosed
with
C-SCLC
are
currently
recommended
to
receive
the
same
treatment
as
cases
in
absence
clear
evidence
suggesting
different
strategies.
The
genomic
profiling
rarely
studied.
Herein,
we
report
case
extensive-stage
harboring
KIF5B-RET
fusion
before
first-line
therapy
persistent
sensitivity
fourth-line
selpercatinib
reported.
Materials
Methods:
Molecular
pathological
features
were
evaluated
using
transbronchial
biopsy,
immunohistochemical
(IHC)
staining
next-generation
sequencing
(NGS).
Results:
NGS
revealed
tumor.
patient
had
progression-free
survival
(PFS)
surpassing
14
months
after
treatment,
ongoing
clinical
response
4th-line
treatment.
Conclusion:
This
highlights
importance
comprehensive
molecular
testing
for
selecting
optimal
Although
RET
patients
C-SCLC,
its
identification
selective
inhibitors
may
contribute
benefits.
Keywords:
combined
cancer,
rearranged
during
transfection,
selpercatinib,