Abstract
Following
the
first
characterization
of
circulating
tumor
DNA
(ctDNA)
in
1990s,
recent
advances
led
to
its
introduction
clinics.
At
present,
European
Society
Of
Medical
Oncology
(ESMO)
recommendations
endorse
ctDNA
testing
routine
clinical
practice
for
genotyping
direct
molecularly
targeted
therapies
patients
with
metastatic
cancer.
In
studies
on
breast
cancer,
has
been
utilized
treatment
tailoring,
tracking
mechanisms
drug
resistance,
and
predicting
disease
response
before
imaging.
We
review
available
evidence
regarding
applications
Journal of Clinical Oncology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 14, 2025
Over
the
past
15
years,
landscape
of
early
phase
clinical
trials
(EPCTs)
has
undergone
a
remarkable
expansion
in
both
quantity
and
intricacy.
The
proliferation
sites,
trials,
sponsors,
contract
research
organizations
surged
exponentially,
marking
significant
shift
conduct.
However,
EPCT
operations
suffer
from
numerous
inefficiencies,
such
as
cumbersome
start-up
processes,
which
are
particularly
critical
when
drug
safety
recommended
II
dose
need
to
be
established
timely
manner.
Networks
consortia
may
overcome
some
these
challenges
enrolling
suitable
patients
streamlining
start-up,
distance
disease
trajectory
come
into
play.
In
this
article,
we
provide
an
overview
adult
oncology
across
different
continents
assembled
through
systematic
review
literature
snowball
sampling
methodology.
We
illustrate
their
scope,
structure,
funding,
achievements.
Fifteen
were
identified
including
two
United
States,
three
Europe,
five
Asia-Pacific,
intercontinental
consortia,
within
private
networks.
These
vary
structure
government-funded
models
National
Cancer
Institute
Experimental
Therapeutics
Clinical
Trials
charitably
funded
organizations.
play
role
collaborative
research,
molecular
tumor
boards
patient-centric
biomarker-matched
treatments,
trial
conduct
improve
timelines
cost
efficiency.
growth
activity
complexity
resulted
number
globally.
By
actively
engaging
with
regulatory
bodies
pharmaceutical
organization
industries,
have
opportunity
address
evolving
faced
field
accelerate
translation
scientific
discoveries
practice.
Frontiers in Oncology,
Год журнала:
2023,
Номер
13
Опубликована: Март 3, 2023
Modern
cancer
therapeutics
are
increasingly
targeted,
bringing
the
promise
of
new
and
improved
activity,
alongside
better
tolerability.
However,
while
many
indeed
resulting
in
dramatic
improvements
disease
control
patient
survival,
short-
long-term
tolerability
has
not
always
accompanied
it.
The
choice
dose
schedule
is
often
upper
range
therapeutic
window,
driven
by
maximum
tolerated
(MTD)
model
previous
cytotoxic
agents.
There
increasing
recognition
that
this
needs
to
change,
taking
a
more
holistic
approach
determine
optimal
for
desired
biological
effects
early
clinical
development.
In
US,
FDA's
Oncology
Centre
Excellence
addressing
via
Project
Optimus
initiative:
aiming
reform
optimisation
studies
so
they
can
demonstrate
most
appropriate
selection.
Early
development
will
need
dose-exposure,
-pharmacodynamic,
-toxicity
-activity
relationships,
including
randomised
evaluations
Regulatory
agencies
outside
US
similarly
exploring
this.
Along
with
Australia,
Brazil,
Canada,
Israel,
Singapore
Switzerland,
UK
participates
Orbis,
collaborative
program
FDA
accelerate
access
medicines
through
coordinated
regulatory
review.
Close
alignment
be
important
internationally
require
changes
across
industry,
academic
units
small
biotech.
We
discuss
our
perspective
on
implications,
opportunities,
phase
oncology
trials
as
uniquely
charity-funded
drug
facility,
Drug
Development
within
Cancer
Research
charity.
Annals of Oncology,
Год журнала:
2024,
Номер
35(11), С. 936 - 953
Опубликована: Авг. 25, 2024
Advances
in
precision
oncology
led
to
approval
of
tumour-agnostic
molecularly
guided
treatment
options
(MGTOs).
The
minimum
requirements
for
claiming
potential
remain
elusive.
CPT Pharmacometrics & Systems Pharmacology,
Год журнала:
2023,
Номер
13(5), С. 691 - 709
Опубликована: Ноя. 16, 2023
Project
Optimus
is
a
US
Food
and
Drug
Administration
Oncology
Center
of
Excellence
initiative
aimed
at
reforming
the
dose
selection
optimization
paradigm
in
oncology
drug
development.
This
project
seeks
to
bring
together
pharmaceutical
companies,
international
regulatory
agencies,
academic
institutions,
patient
advocates,
other
stakeholders.
Although
there
much
promise
this
initiative,
are
several
challenges
that
need
be
addressed,
including
multidimensionality
problem
oncology,
heterogeneity
cancer
patients,
importance
evaluating
long-term
tolerability
beyond
dose-limiting
toxicities,
lack
reliable
biomarkers
for
efficacy.
Through
lens
Totality
Evidence
with
mindset
model-informed
development,
we
offer
insights
into
by
building
quantitative
knowledge
base
integrating
diverse
sources
data
leveraging
modeling
tools
build
evidence
dosage
considering
exposure,
disease
biology,
efficacy,
toxicity,
factors.
We
believe
rational
can
achieved
improving
outcomes
maximizing
therapeutic
benefit
while
minimizing
toxicity.
Journal of Clinical Investigation,
Год журнала:
2024,
Номер
134(12)
Опубликована: Июнь 16, 2024
STING
agonists
can
reprogram
the
tumor
microenvironment
to
induce
immunological
clearance
within
central
nervous
system.
Using
multiplexed
sequential
immunofluorescence
(SeqIF)
and
Ivy
Glioblastoma
Atlas,
expression
was
found
in
myeloid
populations
perivascular
space.
The
agonist
8803
increased
median
survival
multiple
preclinical
models
of
glioblastoma,
including
QPP8,
an
immune
checkpoint
blockade-resistant
model,
where
100%
mice
were
cured.
Ex
vivo
flow
cytometry
profiling
during
therapeutic
window
demonstrated
increases
trafficking
activation,
alongside
enhancement
CD8+
T
cell
NK
effector
responses.
Treatment
with
reprogrammed
microglia
express
costimulatory
CD80/CD86
iNOS,
while
decreasing
immunosuppressive
CD206
arginase.
In
humanized
mice,
is
epigenetically
silenced,
activity
maintained,
further
attesting
dependency
reprogramming.
Although
combination
a
STAT3
inhibitor
did
not
enhance
activity,
addition
anti-PD-1
antibodies
treatment
enhanced
blockade-responsive
glioma
model.
summary,
as
monotherapy
demonstrates
marked
meriting
consideration
for
clinical
translation.
ESMO Open,
Год журнала:
2023,
Номер
8(6), С. 102046 - 102046
Опубликована: Ноя. 16, 2023
Early
phase
cancer
clinical
trials
(EPCTs)
involve
experimental
drugs
being
used
for
the
first
time
in
humans.
These
studies
are
designed
dose
determination
and
safety,
represent
most
intensive
of
all
both
clinicians
patients.
We
sought
to
quantify
amount
patient
consumed
through
EPCT
participation.
