Cancers,
Год журнала:
2025,
Номер
17(2), С. 236 - 236
Опубликована: Янв. 13, 2025
Hepatocellular
carcinoma
(HCC)
is
a
leading
cause
of
cancer-related
mortality
worldwide,
and,
with
only
15-20%
HCC
patients
being
suitable
for
potentially
curative
treatments,
the
vast
majority
ultimately
require
systemic
therapy.
For
decades,
choice
effective
therapy
remained
sparse.
In
recent
years,
after
combination
atezolizumab
and
bevacizumab
demonstrated
superior
overall
survival
over
first-line
standard,
sorafenib,
there
has
been
major
therapeutic
paradigm
shift
to
immunotherapy-based
regimens
HCC.
While
representing
great
leap
forward
treatment
this
cancer,
reality
that
less
than
one-third
achieve
an
objective
response
immune
checkpoint
inhibitor-based
therapy,
so
remains
significant
clinical
need
further
optimization.
review,
we
provide
overview
current
landscape
immunotherapy
unresectable
delve
into
tumor
intrinsic
extrinsic
mechanisms
resistance
established
immunotherapies
focus
on
novel
targets
strong
translational
potential.
Following
this,
spotlight
emerging
approaches
notable
trials
aiming
optimize
efficacy
in
include
inhibitors,
microenvironment
modulators,
targeted
delivery
systems,
locoregional
interventions.
The
antibody–drug
conjugate
(ADC)
field
has
undergone
a
renaissance,
with
substantial
recent
developmental
investment
and
subsequent
drug
approvals
over
the
past
6
y.
In
November
2022,
ElahereTM
became
latest
ADC
to
be
approved
by
US
Food
Drug
Administration
(FDA).
To
date,
260
ADCs
have
been
tested
in
clinic
against
various
oncology
indications.
Here,
we
review
clinical
landscape
of
that
are
currently
FDA
(11),
agents
trials
but
not
yet
(164),
candidates
discontinued
following
testing
(92).
These
clinically
further
analyzed
their
targeting
tumor
antigen(s),
linker,
payload
choices,
highest
stage
achieved,
highlighting
limitations
associated
candidates.
Lastly,
discuss
biologic
engineering
modifications
preclinically
demonstrated
improve
therapeutic
index
if
incorporated
may
increase
proportion
molecules
successfully
transition
regulatory
approval.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(11), С. 9674 - 9674
Опубликована: Июнь 2, 2023
The
treatment
of
cancer
patients
has
dramatically
changed
over
the
past
decades
with
advent
monoclonal
antibodies,
immune-checkpoint
inhibitors,
bispecific
and
innovative
T-cell
therapy.
Antibody-drug
conjugates
(ADCs)
have
also
revolutionized
cancer.
Several
ADCs
already
been
approved
in
hematology
clinical
oncology,
such
as
trastuzumab
emtansine
(T-DM1),
deruxtecan
(T-DXd),
sacituzumab
govitecan
(SG)
for
metastatic
breast
cancer,
enfortumab
vedotin
(EV)
urothelial
carcinoma.
efficacy
is
limited
by
emergence
resistance
due
to
different
mechanisms,
antigen-related
resistance,
failure
internalization,
impaired
lysosomal
function,
other
mechanisms.
In
this
review,
we
summarize
data
that
contributed
approval
T-DM1,
T-DXd,
SG,
EV.
We
discuss
mechanisms
ADCs,
well
ways
overcome
combination
inhibitors
or
tyrosine-kinase
inhibitors.
Bioconjugate Chemistry,
Год журнала:
2023,
Номер
34(11), С. 1951 - 2000
Опубликована: Окт. 11, 2023
Antibody–drug
conjugates
(ADCs)
are
targeted
immunoconjugate
constructs
that
integrate
the
potency
of
cytotoxic
drugs
with
selectivity
monoclonal
antibodies,
minimizing
damage
to
healthy
cells
and
reducing
systemic
toxicity.
Their
design
allows
for
higher
doses
drug
be
administered,
potentially
increasing
efficacy.
They
currently
among
most
promising
classes
in
oncology,
efforts
expand
their
application
nononcological
indications
combination
therapies.
Here
we
provide
a
detailed
overview
recent
advances
ADC
research
consider
future
directions
challenges
promoting
this
platform
widespread
therapeutic
use.
We
examine
data
from
CAS
Content
Collection,
largest
human-curated
collection
published
scientific
information,
analyze
publication
landscape
reveal
exploration
trends
documents
insights
into
area.
also
discuss
evolution
key
concepts
field,
major
technologies,
development
pipelines
company
focuses,
disease
targets,
stages,
investment
trends.
A
comprehensive
concept
map
has
been
created
based
on
Collection.
hope
report
can
serve
as
useful
resource
understanding
current
state
knowledge
field
ADCs
remaining
fulfill
potential.
Cancers,
Год журнала:
2023,
Номер
15(4), С. 1278 - 1278
Опубликована: Фев. 17, 2023
Antibody–drug
conjugates
(ADCs),
with
antibodies
targeted
against
specific
antigens
linked
to
cytotoxic
payloads,
offer
the
opportunity
for
a
more
delivery
of
chemotherapy
and
other
bioactive
payloads
minimize
side
effects.
First
approved
in
setting
HER2+
breast
cancer,
recent
ADCs
have
been
developed
triple-negative
cancer
(TNBC)
and,
most
recently,
hormone
receptor-positive
(HR+)
cancer.
While
antibody–drug
compared
favorably
traditional
some
settings,
patients
eventually
progress
on
these
therapies
require
change
treatment.
Mechanisms
explain
resistance
are
highly
sought
after,
hopes
developing
next-line
treatment
options
expanding
therapeutic
windows
existing
therapies.
These
mechanisms
categorized
as
follows:
antigen
expression,
ADC
processing
resistance,
efflux
payload.
This
paper
reviews
recently
published
literature
well
potential
overcome
barriers.
Cancers,
Год журнала:
2024,
Номер
16(2), С. 447 - 447
Опубликована: Янв. 20, 2024
Introduced
almost
two
decades
ago,
ADCs
have
marked
a
breakthrough
in
the
targeted
therapy
era,
providing
clinical
benefits
to
many
cancer
patients.
While
inherent
complexity
of
this
class
drugs
has
challenged
their
development
and
broad
application,
experience
gained
from
years
trials
errors
recent
advances
construct
design
delivery
led
an
increased
number
approved
or
late
only
five
years.
Target
payload
diversification,
along
with
novel
conjugation
linker
technologies,
are
at
forefront
next-generation
ADC
development,
renewing
hopes
broaden
scope
these
difficult-to-treat
cancers
beyond.
This
review
highlights
trends
field,
focusing
on
mechanism
action
implications
ADCs’
therapeutic
profile.
The
evolution
conventional
innovative
formats
will
be
illustrated,
some
current
hurdles,
including
toxicity
drug
resistance.
Future
directions
improve
also
presented.
