Clinical Cancer Research,
Journal Year:
2023,
Volume and Issue:
30(4), P. 836 - 848
Published: Dec. 7, 2023
Abstract
Purpose:
Genomic
rearrangements
can
generate
potent
oncogenic
drivers
or
disrupt
tumor
suppressor
genes.
This
study
examines
the
landscape
of
fusions
and
detected
by
liquid
biopsy
(LBx)
circulating
DNA
(ctDNA)
across
different
cancer
types.
Experimental
Design:
LBx
from
53,842
patients
with
66
solid
types
were
profiled
using
FoundationOneLiquid
CDx,
a
hybrid-capture
sequencing
platform
that
queries
324
cancer-related
Tissue
biopsies
(TBx)
FoundationOneCDx
used
as
comparator.
Results:
Among
all
LBx,
7,377
(14%)
had
≥1
pathogenic
rearrangement
detected.
A
total
3,648
(6.8%)
gain-of-function
(GOF)
oncogene
rearrangement,
4,428
(8.2%)
loss-of-function
Cancer
higher
prevalence
GOF
included
those
canonical
fusion
drivers:
prostate
(19%),
cholangiocarcinoma
(6.4%),
bladder
(5.5%),
non–small
cell
lung
(4.4%).
Although
driver
was
lower
in
than
TBx
overall,
frequency
detection
comparable
fraction
(TF)
≥1%.
Rearrangements
FGFR2,
BRAF,
RET,
ALK,
types,
but
tended
to
be
clonal
variants
some
potential
acquired
resistance
others.
Conclusions:
In
contrast
prior
literature,
this
reports
wide
variety
ctDNA.
The
tissue
when
TF
presents
viable
alternative
is
not
available,
there
may
less
value
confirmatory
testing
sufficient.
Annals of Oncology,
Journal Year:
2024,
Volume and Issue:
35(7), P. 588 - 606
Published: May 27, 2024
Advancements
in
the
field
of
precision
medicine
have
prompted
European
Society
for
Medical
Oncology
(ESMO)
Precision
Medicine
Working
Group
to
update
recommendations
use
tumour
next-generation
sequencing
(NGS)
patients
with
advanced
cancers
routine
practice.
Cancer Discovery,
Journal Year:
2023,
Volume and Issue:
13(9), P. 2012 - 2031
Published: June 4, 2023
Abstract
Oncogenic
activation
of
fibroblast
growth
factor
receptor
2
(FGFR2)
drives
multiple
cancers
and
represents
a
broad
therapeutic
opportunity,
yet
selective
targeting
FGFR2
has
not
been
achieved.
Although
the
clinical
efficacy
pan-FGFR
inhibitors
(pan-FGFRi)
validates
driver
status
in
fusion–positive
intrahepatic
cholangiocarcinoma,
their
benefit
is
limited
by
incomplete
target
coverage
due
to
FGFR1-
FGFR4-mediated
toxicities
(hyperphosphatemia
diarrhea,
respectively)
emergence
resistance
mutations.
RLY-4008
highly
selective,
irreversible
inhibitor
designed
overcome
these
limitations.
In
vitro,
demonstrates
>250-
>5,000-fold
selectivity
over
FGFR1
FGFR4,
respectively,
targets
primary
alterations
vivo,
induces
regression
xenograft
models—including
models
with
mutations
that
drive
progression
on
current
pan-FGFRi—while
sparing
FGFR4.
early
testing,
induced
responses
without
clinically
significant
off-isoform
FGFR
toxicities,
confirming
potential
targeting.
Significance:
Patients
FGFR2-driven
derive
from
pan-FGFRi
FGFR1–4-mediated
acquired
tumor
while
other
FGFRs,
suggesting
it
may
have
potential.
See
related
commentary
Tripathi
et
al.,
p.
1964.
This
article
featured
Selected
Articles
Issue,
1949
Liver International,
Journal Year:
2023,
Volume and Issue:
43(8), P. 1803 - 1812
Published: July 14, 2023
Abstract
Background
The
TOPAZ‐1
phase
III
trial
reported
a
survival
benefit
with
the
anti‐programmed
death
cell
ligand
1
(anti‐PD‐L1)
durvalumab
in
combination
gemcitabine
and
cisplatin
patients
advanced
biliary
tract
cancer.
present
study
investigated
efficacy
safety
of
this
new
standard
treatment
real‐world
setting.
Methods
analysed
population
included
unresectable,
locally
or
metastatic
adenocarcinoma
treated
at
17
Italian
centres.
primary
endpoint
was
progression‐free
(PFS),
whereas
secondary
endpoints
overall
(OS),
response
rate
(ORR)
safety.
Unadjusted
adjusted
hazard
ratios
(HRs)
by
baseline
characteristics
were
calculated
using
Cox
proportional
hazards
model.
Results
From
February
2022
to
November
2022,
145
enrolled.
After
median
follow‐up
8.5
months
(95%
CI:
7.9–13.6),
PFS
8.9
7.4–11.7).
Median
OS
12.9
10.9–12.9).
investigator‐assessed
confirmed
ORR
34.5%,
disease
control
87.6%.
Any
grade
adverse
events
(AEs)
occurred
137
(94.5%).
Grades
3–4
AEs
51
(35.2%).
immune‐mediated
(imAEs)
22.7%.
imAEs
2.1%
patients.
In
univariate
analysis,
non‐viral
aetiology,
ECOG
PS
>0
NLR
≥3
correlated
shorter
PFS.
Conclusion
results
first
analysis
mostly
achieved
terms
PFS,
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: March 4, 2024
Abstract
In
the
era
of
precision
medicine,
it
has
been
increasingly
recognized
that
individuals
with
a
certain
disease
are
complex
and
different
from
each
other.
Due
to
underestimation
significant
heterogeneity
across
participants
in
traditional
“one-size-fits-all”
trials,
patient-centered
trials
could
provide
optimal
therapy
customization
specific
biomarkers
were
developed
including
basket,
umbrella,
platform
trial
designs
under
master
protocol
framework.
recent
years,
successive
FDA
approval
indications
based
on
biomarker-guided
demonstrated
these
new
clinical
ushering
tremendous
opportunities.
Despite
rapid
increase
number
current
research
understanding
designs,
as
compared
remains
limited.
The
majority
focuses
methodologies,
there
is
lack
in-depth
insight
concerning
underlying
biological
logic
designs.
Therefore,
we
this
comprehensive
review
discovery
development
their
perspective
medicine.
Meanwhile,
discuss
future
directions
potential
design
view
“Precision
Pro”,
“Dynamic
Precision”,
“Intelligent
Precision”.
This
would
assist
trial-related
researchers
enhance
innovation
feasibility
by
expounding
logic,
which
be
essential
accelerate
progression
