Virchows Archiv,
Journal Year:
2023,
Volume and Issue:
484(2), P. 169 - 179
Published: Nov. 20, 2023
Abstract
Medical
oncology
is
rapidly
evolving
with
the
implementation
of
personalized,
targeted
therapies.
Advances
in
molecular
diagnostics
and
biologic
understanding
cancer
pathophysiology
led
to
identification
specific
genetic
alterations
as
drivers
progression.
Further,
improvements
drug
development
enable
direct
interference
these
pathways,
which
allow
tailoring
personalized
treatments
based
on
a
distinct
characterization
tumors.
Thereby,
we
are
currently
experiencing
paradigm-shift
treatment
cancers
towards
cancer-type
agnostic,
molecularly
targeted,
However,
this
concept
has
several
important
hurdles
limitations
overcome
ultimately
increase
proportion
patients
benefitting
from
precision
approach.
These
include
assessment
clinical
relevancy
identified
alterations,
capturing
interpreting
levels
heterogeneity
intra-tumoral
or
time-dependent
evolution,
challenges
practical
routine
care.
In
present
review,
summarize
current
state
cancer-agnostic
oncology,
discuss
tumor
boards,
consider
therapy.
provide
an
outlook
potential
future
developments
including
functionality
assessments
broader
use
liquid
biopsies
order
obtain
more
comprehensive
longitudinal
information
that
might
guide
therapy
future.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Jan. 1, 2024
Abstract
Combining
existing
drug
therapy
is
essential
in
developing
new
therapeutic
agents
disease
prevention
and
treatment.
In
preclinical
investigations,
combined
effect
of
certain
known
drugs
has
been
well
established
treating
extensive
human
diseases.
Attributed
to
synergistic
effects
by
targeting
various
pathways
advantages,
such
as
reduced
administration
dose,
decreased
toxicity,
alleviated
resistance,
combinatorial
treatment
now
being
pursued
delivering
combat
major
clinical
illnesses,
cancer,
atherosclerosis,
pulmonary
hypertension,
myocarditis,
rheumatoid
arthritis,
inflammatory
bowel
disease,
metabolic
disorders
neurodegenerative
Combinatorial
involves
combining
or
co-delivering
two
more
for
a
specific
disease.
Nanoparticle
(NP)-mediated
delivery
systems,
i.e.,
liposomal
NPs,
polymeric
NPs
nanocrystals,
are
great
interest
wide
range
due
targeted
delivery,
extended
release,
higher
stability
avoid
rapid
clearance
at
infected
areas.
This
review
summarizes
targets
diseases,
clinically
approved
combinations
the
development
multifunctional
emphasizes
strategies
based
on
severe
Ultimately,
we
discuss
challenging
NP-codelivery
translation
provide
potential
approaches
address
limitations.
offers
comprehensive
overview
recent
cutting-edge
NP-mediated
combination
Journal of Clinical Oncology,
Journal Year:
2024,
Volume and Issue:
42(20), P. 2446 - 2455
Published: April 24, 2024
PURPOSE
The
anti-NECTIN4
antibody-drug
conjugate
enfortumab
vedotin
(EV)
is
approved
for
patients
with
metastatic
urothelial
cancer
(mUC).
However,
durable
benefit
only
achieved
in
a
small,
yet
uncharacterized
patient
subset.
NECTIN4
located
on
chromosome
1q23.3,
and
1q23.3
gains
represent
frequent
copy
number
variations
(CNVs)
cancer.
Here,
we
aimed
to
evaluate
amplifications
as
genomic
biomarker
predict
EV
response
mUC.
MATERIALS
AND
METHODS
We
established
NECTIN4-specific
fluorescence
situ
hybridization
(FISH)
assay
assess
the
predictive
value
of
CNVs
multicenter
EV-treated
mUC
cohort
(mUC-EV,
n
=
108).
were
correlated
membranous
protein
expression,
treatment
responses,
outcomes.
also
assessed
prognostic
measured
biopsies
non–EV-treated
(mUC-non-EV,
103).
Furthermore,
queried
Cancer
Genome
Atlas
(TCGA)
data
sets
(10,712
across
32
types)
CNVs.
RESULTS
are
events
muscle-invasive
bladder
(TCGA
set:
approximately
17%)
(approximately
26%
our
cohorts).
In
mUC-EV,
amplification
represents
stable
alteration
during
progression
associates
enhanced
expression.
Ninety-six
percent
(27
28)
demonstrated
objective
responses
compared
32%
(24
74)
nonamplified
subgroup
(
P
<
.001).
multivariable
Cox
analysis
adjusted
age,
sex,
Bellmunt
risk
factors,
led
92%
reduction
death
(hazard
ratio,
0.08
[95%
CI,
0.02
0.34];
mUC-non-EV,
not
associated
TCGA
Pan-Cancer
that
occur
frequently
other
cancers,
example,
5%-10%
breast
lung
cancers.
CONCLUSION
predictors
long-term
survival
Clinical Cancer Research,
Journal Year:
2023,
Volume and Issue:
29(15), P. 2753 - 2760
Published: April 6, 2023
Biomarker-driven
cancer
therapy
has
revolutionized
precision
oncology.
With
a
better
understanding
of
tumor
biology,
tissue-agnostic
targets
have
been
characterized
and
explored,
which
ultimately
led
to
therapeutics
with
pan-cancer
efficacy.
To
date,
five
molecular
biomarkers
obtained
FDA
approval
for
targeted
therapies
immunotherapies.
Those
include
BRAFV600E
mutations,
RET
fusions,
NTRK
high
mutation
burden
(TMB),
deficient
mismatch
repair/high
microsatellite
instability
(dMMR/MSI-High).
Herein,
we
used
data
from
AACR
project
GENIE
explore
the
clinico-genomic
landscape
these
alterations.
is
publicly
accessible
registry
genomic
multiple
collaborating
centers.
Current
database
(version
13.0)
includes
sequencing
168,423
samples
collected
patients
different
cancers.
We
were
able
identify
BRAFV600E,
TMB
in
2.9%,
1.6%,
1.5%,
15.2%
samples,
respectively.
In
this
article,
describe
distribution
those
among
types.
addition,
summarize
current
prospect
on
biology
alterations
evidence
approved
drugs,
including
pembrolizumab,
dostarilmab,
larotrectinib,
entrectinib,
selpercatinib,
dabrafenib/trametinib
combination.
Biomarker Research,
Journal Year:
2023,
Volume and Issue:
11(1)
Published: July 19, 2023
Abstract
Biomarkers
are
detectable
molecules
that
can
reflect
specific
physiological
states
of
cells,
organs,
and
organisms
therefore
be
regarded
as
indicators
for
diseases.
And
the
discovery
biomarkers
plays
an
essential
role
in
cancer
management
from
initial
diagnosis
to
final
treatment
regime.
Practically,
reliable
clinical
still
limited,
restricted
by
suboptimal
methods
biomarker
discovery.
Nucleic
acid
aptamers
nowadays
could
used
a
powerful
tool
protein
biomarkers.
single-strand
oligonucleotides
specifically
bind
various
targets
with
high
affinity.
As
artificial
ssDNA
or
RNA,
possess
unique
advantages
compared
conventional
antibodies.
They
flexible
design,
low
immunogenicity,
relative
chemical/thermos
stability,
well
modifying
convenience.
Several
SELEX
(Systematic
Evolution
Ligands
Exponential
Enrichment)
based
have
been
generated
recently
construct
discovering
new
different
cell
locations.
Secretome
SELEX-based
selection
facilitate
identification
secreted
The
developed
cell-SELEX
unveil
those
presented
on
surface.
tissue-SELEX
target
intracellular
multiplexed
detection
technology,
aptamer-based
SOMAScan
analyze
thousands
proteins
single
run.
In
this
review,
we
will
introduce
principle
workflow
variations
methods,
including
secretome
SELEX,
ADAPT,
Cell-SELEX
tissue
SELEX.
Another
proteome
analyzing
tool,
SOMAScan,
also
covered.
second
half
how
these
accelerate
diseases,
cardiovascular
neurodegenerative
discussed.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(21), P. 15787 - 15787
Published: Oct. 31, 2023
The
Warburg
effect
is
the
long-standing
riddle
of
cancer
biology.
How
does
aerobic
glycolysis,
inefficient
in
producing
ATP,
confer
a
growth
advantage
to
cells?
A
new
evaluation
large
set
literature
findings
covering
and
its
yeast
counterpart,
Crabtree
effect,
led
an
innovative
working
hypothesis
presented
here.
It
holds
that
enhanced
glycolysis
partially
inactivates
oxidative
phosphorylation
induce
functional
rewiring
TCA
cycle
enzymes
generate
non-canonical
metabolic
pathways
sustain
faster
rates.
has
been
structured
by
constructing
two
maps,
one
for
metabolism
other
effect.
New
lines
investigation,
suggested
these
are
discussed
as
instrumental
leading
toward
better
understanding
biology
order
allow
development
more
efficient
metabolism-targeted
anticancer
drugs.
Frontiers in Genetics,
Journal Year:
2023,
Volume and Issue:
14
Published: March 10, 2023
Diagnostics
require
precision
and
predictive
ability
to
be
clinically
useful.
Integration
of
multi-omic
with
clinical
data
is
crucial
our
understanding
disease
pathogenesis
diagnosis.
However,
interpretation
overwhelming
amounts
information
at
the
individual
level
requires
sophisticated
computational
tools
for
extraction
meaningful
outputs.
Moreover,
evolution
technical
analytical
methods
often
outpaces
standardisation
strategies.
RNA
most
dynamic
component
all
-omics
technologies
carrying
an
abundance
regulatory
that
least
harnessed
use
in
diagnostics.
Gene
expression-based
tests
capture
genetic
non-genetic
heterogeneity
have
been
implemented
certain
diseases.
For
example
patients
early
breast
cancer
are
spared
toxic
unnecessary
treatments
scores
based
on
expression
a
set
genes
(e.g.,
Oncotype
DX).
The
transcriptomics
portray
transcriptional
status
moment
time
has
also
used
diagnosis
diseases
such
as
sepsis.
profiles
identify
endotypes
sepsis
prognostic
value
potential
discriminate
between
viral
bacterial
infection.
application
patient
stratification
environments
trials
thus
holds
promise.
In
this
review,
we
discuss
current
fields
We
these
paradigms
highlight
impediments
identifying
useful
diagnostic
biomarkers
propose
approaches
overcome
them
aid
efforts
towards
implementation.
