Cellular & Molecular Biology Letters,
Год журнала:
2024,
Номер
29(1)
Опубликована: Апрель 10, 2024
Melanoma
is
the
most
lethal
skin
cancer
characterized
by
its
high
metastatic
potential.
In
past
decade,
targeted
and
immunotherapy
have
brought
revolutionary
survival
benefits
to
patients
with
advanced
melanoma,
but
these
treatment
responses
are
also
heterogeneous
and/or
do
not
achieve
durable
responses.
Therefore,
novel
therapeutic
strategies
for
improving
outcomes
remain
an
unmet
clinical
need.
The
aim
of
this
study
was
evaluate
potential
underlying
molecular
mechanisms
RC48,
a
HER2-target
antibody
drug
conjugate,
either
alone
or
in
combination
dabrafenib,
V600-mutant
BRAF
inhibitor,
BRAF-mutant
cutaneous
melanoma.
Pediatric and Developmental Pathology,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 7, 2025
Pediatric
pancreatic
acinar
cell
carcinoma
(PACC)
is
a
rare
malignancy,
comprising
5-15%
of
pediatric
tumors.
BRAF
rearrangement
found
in
20%–30%
PACC
cases.
We
report
case
with
novel
GLCCI1::BRAF
fusion
and
independent
amplifications
MYC
MYCN
.
A
10-year-old
male
presented
6
months
weight
loss,
back
pain,
loose
stools.
Imaging
demonstrated
concentric
soft
tissue
thickening
around
the
superior
mesenteric
artery,
prompting
biopsy
periaortic
lymph
node
showing
metastatic
PACC.
Pancreaticoduodenectomy
revealed
deposits
multiple
nodes
retroperitoneal
tissue.
Fluorescence
situ
hybridization
both
pancreaticoduodenectomy
specimens
gene
rearrangement,
partner
identified
as
GLCCI1
by
next
generation
sequencing
assays.
Chromosomal
microarray
analysis
amplification
resection
specimen.
The
patient
was
treated
neoadjuvant
chemotherapy,
radiation,
pan-RAF
inhibitor,
but
developed
new
widespread
metastasis
deceased
22
after
presentation.
combination
primary
secondary
likely
to
drive
aggressive
behavior
this
npj Precision Oncology,
Год журнала:
2024,
Номер
8(1)
Опубликована: Март 4, 2024
Abstract
Head
and
neck
cancer
is
a
major
cause
of
morbidity
mortality
worldwide.
The
identification
genetic
alterations
in
head
may
improve
diagnosis
treatment
outcomes.
In
this
study,
we
report
the
functional
characterization
UBE3C-LRP5
translocation
cancer.
Our
whole
transcriptome
sequencing
RT-PCR
analysis
151
tumor
samples
identified
LRP5-UBE3C
fusion
transcripts
5.3%
patients
Indian
origin
(
n
=
151),
1.2%
TCGA-HNSC
502).
Further,
genome
breakpoint
translocation.
We
demonstrate
that
activating
vitro
vivo,
promotes
proliferation,
migration,
invasion
cells.
contrast,
depletion
suppresses
clonogenic,
migratory,
invasive
potential
activates
Wnt/β-catenin
signaling
by
promoting
nuclear
accumulation
β-catenin,
leading
to
upregulation
target
genes,
MYC,
CCND1,
TCF4
,
LEF1
.
Consistently,
with
FDA-approved
drug,
pyrvinium
pamoate,
significantly
reduced
transforming
ability
cells
expressing
protein
improved
survival
mice
bearing
tumors
fusion-overexpressing
Interestingly,
fusion-expressing
upon
knockdown
CTNNB1
or
show
clonogenic
abilities,
sensitivity
pamoate.
Overall,
our
study
suggests
promising
therapeutic
for
pamoate
be
drug
candidate
treating
harboring
Cellular & Molecular Biology Letters,
Год журнала:
2024,
Номер
29(1)
Опубликована: Апрель 10, 2024
Melanoma
is
the
most
lethal
skin
cancer
characterized
by
its
high
metastatic
potential.
In
past
decade,
targeted
and
immunotherapy
have
brought
revolutionary
survival
benefits
to
patients
with
advanced
melanoma,
but
these
treatment
responses
are
also
heterogeneous
and/or
do
not
achieve
durable
responses.
Therefore,
novel
therapeutic
strategies
for
improving
outcomes
remain
an
unmet
clinical
need.
The
aim
of
this
study
was
evaluate
potential
underlying
molecular
mechanisms
RC48,
a
HER2-target
antibody
drug
conjugate,
either
alone
or
in
combination
dabrafenib,
V600-mutant
BRAF
inhibitor,
BRAF-mutant
cutaneous
melanoma.
