Cancer,
Год журнала:
2023,
Номер
130(S8), С. 1371 - 1377
Опубликована: Ноя. 3, 2023
Abstract
Antibody
drug
conjugates
(ADCs)
are
novel
drugs
that
exert
specific
cytotoxicity
against
tumor
cells.
China
approved
T‐Dxd
in
May
2023,
and
their
introduction
has
changed
the
nation’s
clinical
practice.
Although
more
than
700
ADCs
being
investigated
worldwide,
challenges
remain
antibody
engineering,
discovery,
safety
management,
resistance,
selection,
sequencing
hinder
further
promotion
application
of
ADCs.
Experts
have
discussed
several
critical
concerns
related
to
practice
since
2022.
Here,
authors
conducted
a
review
then
explored
China.
This
study
proposes
solutions
strategies
maximize
potential
benefit
can
provide
patients
with
breast
cancer.
Cancer Biology and Medicine,
Год журнала:
2024,
Номер
unknown, С. 1 - 15
Опубликована: Июнь 25, 2024
Angiogenesis
is
considered
a
hallmark
pathophysiological
process
in
tumor
development.
Aberrant
vasculature
resulting
from
angiogenesis
plays
critical
role
the
development
of
resistance
to
breast
cancer
treatments,
The Oncologist,
Год журнала:
2024,
Номер
29(8), С. e957 - e966
Опубликована: Апрель 4, 2024
Abstract
Background
The
optimal
sequential
strategy
for
antibody-drug
conjugates
(ADCs)
in
breast
cancer
remains
uncertain.
This
study
aimed
to
evaluate
the
efficacy
and
potential
resistance
of
second
ADC
(ADC2)
following
first
(ADC1)
human
epidermal
growth
factor
receptor
2
(HER2)-positive
HER2-low
MBC.
Methods
retrospective,
multicenter,
real-world
enrolled
patients
with
MBC
who
received
at
least
different
types
ADCs
3
hospitals
China
between
July
1,
2017
May
2023.
Outcomes
included
objective
response
rate
(ORR)
ADC1
ADC2,
progression
free
survival
(PFS2),
defined
as
time
from
initiation
ADC2
progression,
overall
(OS).
Results
Seventy-nine
female
were
included,
64
whom
had
HER2-positive
disease.
ORR
similar
payload
was
found
be
5.3%.
When
switching
a
payload,
increased
22.6%.
PFS2
remained
regardless
whether
or
different.
Switching
showed
higher
rapid
durable
longer
than
6
months
(41.2%
vs
15.0%).
Specifically,
significantly
OS
seen
treated
trastuzumab
deruxtecan
(T-Dxd)
compared
those
disitamab
vedotin
(RC48)
after
emtansine
(T-DM1;
median
5.37
3.30
months,
HR
=
0.40,
95%
CI
0.17-0.93,
P
.034;
50.6
20.2
0.27,
0.08-0.91,
.034).
For
progressed
T-Dxd,
6.05
RC48
versus
0.93
T-DM1
(HR
0.03,
0.002-0.353,
.0093).
Genomic
analysis
revealed
that
alternation
retinoblastoma1
associated
superior
PFS.
Conclusion
achieves
responses
settings.
T-Dxd
followed
by
may
potentially
beneficial
Further
research
is
needed
elucidate
mechanism
cross-resistance.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 9, 2025
Antibody-drug
conjugates
(ADCs)
are
an
emerging
strategy
in
cancer
therapy,
enhancing
precision
and
efficacy
by
linking
targeted
antibodies
to
potent
cytotoxic
agents.
This
study
introduces
a
novel
ADC
that
combines
ribonuclease
A
(RNase
A)
with
cetuximab
(Cet),
anti-EGFR
monoclonal
antibody,
through
polyethylene
glycol
(PEG)
linker
(RN-PEG-Cet),
aimed
induce
apoptosis
KRAS
mutant
colorectal
(CRC)
via
ROS-mediated
pathway.
RN-PEG-Cet
was
successfully
synthesized
characterized
for
its
physicochemical
properties,
retaining
full
enzymatic
activity
RNA
degradation
high
binding
affinity
EGFR.
In
SW-480
cells,
significantly
reduced
cell
viability
at
lower
doses,
IC50
of
11.7
µg/mL
72
h.
Compared
free
Cet,
demonstrated
~
2-fold
increase
3.5-fold
ROS
production.
The
conjugate
also
disrupted
the
Nrf2/Keap1
pathway,
significant
upregulation
Keap1
(FC
=
3.7,
p
≤
0.01)
downregulation
Nrf2
3.3,
<
0.01),
highlighting
role
impairing
antioxidant
defenses
promoting
cytotoxicity.
These
findings
emphasize
potential
as
therapeutic
approach
CRC,
offering
superior
induction
cytotoxicity
compared
conventional
therapies.
could
represent
new
improving
CRC
treatment
outcomes
effectively
overcoming
resistance
mechanisms.
Surface
antigen-directed
immunotherapy
is
a
curative
treatment
modality
for
acute
myeloid
leukemia
(AML)
that
characterized
by
the
abundance
and
stability
expression
of
surface
antigens.
However,
current
immunotherapies
have
shown
poor
outcomes
undesirable
mortality
rates
in
treating
AML
patients,
primarily
due
to
acquired
resistance
arises
from
using
single-target
therapies
address
heterogeneous
Hence,
order
improve
efficacy
antigen-specific
AML,
we
designed
bispecific
aptamer-drug
conjugate.
In
particular,
cell-SELEX
incorporating
cell
lysate-SELEX
aptamers
with
HEL
cells
yielded
AptCD117,
which
specifically
binds
CD117
(a
highly
expressed
marker
on
both
hematopoietic
stem
primary
cells)
has
excellent
performance
targeting
human
cells.
Combined
CD71-binding
aptamer
LXD-11b
(another
broadly
antigen
cells),
were
couple
monomethyl
auristatin
F
(MMAF)
fabricating
conjugates.
Results
demonstrated
aptamer-MMAF
conjugates
efficiently
kill
different
CD71
levels
target
lines
vitro.
Importantly,
exposure
marrow
specimens
resulted
selective
elimination
vitro
had
no
effect
healthy
lymphocytes
within
same
specimens.
Thus,
these
results
provide
proof
concept
generation
directed
against
cells,
hold
promise
advancing
strategies
improving
patient
outcomes.
Cancer Drug Resistance,
Год журнала:
2024,
Номер
unknown
Опубликована: Май 24, 2024
Human
epidermal
growth
factor
2
(HER2)-positive
breast
cancer
(BC)
represents
nearly
20%
of
all
tumors.
Historically,
these
patients
had
a
high
rate
relapse
and
dismal
prognosis.
The
advent
HER2-targeting
monoclonal
antibodies
such
as
trastuzumab
followed
by
pertuzumab
improved
the
prognosis
HER2-positive
metastatic
BC.
More
recently,
antibody-drug
conjugates
(ADCs)
are
now
reshaping
treatment
paradigm
solid
tumors,
especially
cancer.
Tratsuzumab
emtansine
(T-DM1)
was
one
first
ADC
developed
in
oncology
approved
for
management
In
head-to-head
comparison,
deruxtecan
(T-DXd)
defeated
T-DM1
second-line
treatment.
efficacy
ADCs
is
counterbalanced
appearance
acquired
resistance
to
agents.
this
paper,
we
summarize
mechanisms
action
T-DXd,
well
their
clinical
efficacy.
Additionally,
also
discuss
potential
strategies
addressing
ADC.
Bioengineering & Translational Medicine,
Год журнала:
2024,
Номер
9(6)
Опубликована: Май 4, 2024
Abstract
Antibody‐drug
conjugates
(ADCs),
chemotherapeutic
agents
conjugated
to
an
antibody
enhance
their
targeted
delivery
tumors,
represent
a
significant
advancement
in
cancer
therapy.
ADCs
combine
the
precise
targeting
capabilities
of
antibodies
and
potent
cell‐killing
effects
chemotherapy,
allowing
for
enhanced
cytotoxicity
tumors
while
minimizing
damage
healthy
tissues.
Here,
we
provide
overview
current
clinical
landscape
ADCs,
highlighting
11
U.S.
Food
Drug
Administration
(FDA)‐approved
products
discussing
over
500
active
trials
investigating
newer
ADCs.
We
also
discuss
some
key
challenges
associated
with
translation
highlight
emerging
strategies
overcome
these
hurdles.
Our
discussions
will
useful
guidelines
future
development
safer
more
effective
broader
range
indications.
Biomedicines,
Год журнала:
2024,
Номер
12(3), С. 500 - 500
Опубликована: Фев. 23, 2024
Based
on
the
unprecedented
results
observed
in
recent
clinical
trials,
antibody-drug
conjugates
(ADCs)
have
revolutionized
treatment
algorithm
of
metastatic
breast
cancer
(mBC).
The
strategy
sequencing
different
ADCs
other
lines
therapy
is
highly
attractive,
but
proportion
patients
who
undergone
such
a
context
published
trials
still
limited,
especially
for
modern
ADCs.
HER2-positive
disease
primarily
managed
with
sequence
Historically,
trastuzumab
emtansine
(T-DM1)
has
been
most
commonly
used
ADC
both
early
and
disease.
Considering
evidence
related
to
deruxtecan
(T-DXd),
it
expected
assume
role
main
our
practice.
Herein,
we
report
retrospective
analysis
relying
available
data
from
trials.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(13), С. 7131 - 7131
Опубликована: Июнь 28, 2024
Colorectal
cancer
(CRC)
is
the
second
leading
cause
of
cancer-related
death
worldwide.
Therefore,
need
for
new
therapeutic
strategies
still
a
challenge.
Surgery
and
chemotherapy
represent
first-line
interventions;
nevertheless,
prognosis
metastatic
CRC
(mCRC)
patients
remains
unacceptable.
An
important
step
towards
targeted
therapy
came
from
inhibition
epidermal
growth
factor
receptor
(EGFR)
pathway,
by
anti-EGFR
antibody,
Cetuximab,
or
specific
tyrosine
kinase
inhibitors
(TKI).
mouse-human
chimeric
monoclonal
antibody
(mAb),
binds
to
extracellular
domain
EGFR
thus
impairing
EGFR-mediated
signaling
reducing
cell
proliferation.
TKI
can
affect
biochemical
pathway
at
different
steps
along
cascade.
Apart
other
mAbs
have
been
developed,
such
as
Panitumumab.
Both
antibodies
approved
treatment
KRAS-NRAS
wild
type
mCRC,
alone
in
combination
with
chemotherapy.
These
display
strong
differences
activating
host
immune
system
against
CRC,
due
their
immunoglobulin
isotypes.
Although
are
efficient,
drug
resistance
occurs
high
frequency.
Resistant
tumor
populations
either
already
be
present
before
develop
later
adaptations
genomic
mutations
pathway.
Numerous
efforts
made
improve
efficacy
find
agents
that
able
block
downstream
cascade
molecules.
Indeed,
we
examined
importance
analyzing
antibody-drug
conjugates
(ADC)
developed
overcome
and/or
stimulate
host's
immunity
growth.
Also,
patient-derived
organoid
cultures
useful
feasible
vitro
model
study
behavior
response.
Organoids
reflect
genetic
heterogeneity
found
tissue
origin,
representing
unique
tool
personalized
medicine.
Thus,
CRC-derived
smart
studying
microenvironment
preclinical
assay
drugs.
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Янв. 22, 2025
Background
Breast
cancer
(BRCA)
has
a
high
incidence
among
women,
with
poor
prognosis
and
mortality,
which
is
increasing
year
by
year.
Efferocytosis
process
of
phagocytosis
abnormal
cells
great
value
in
tumor
research.
Our
study
seeks
to
create
predictive
model
for
BRCA
using
efferocytosis-related
genes
(ERGs)
explore
the
significance
efferocytosis
this
disease.
Methods
In
research,
Differential
analysis,
univariate
Cox
regression
were
employed
identify
linked
patients.
Then
patients
categorized
into
distinct
groups
consensus
clustering
based
on
genes.
Survival
PCA,
t-SNE
performed
verify
these
groups.
The
enrichment
metabolic
pathways
within
detected
clusters
was
evaluated
gene
set
variation
analysis
(GSVA)
(GSEA).
Additionally,
single-sample
GSEA
(ssGSEA)
used
examine
changes
immune
infiltration
enrichment.
A
risk
prognostic
constructed
utilizing
multivariable
Least
Absolute
Shrinkage
Selection
Operator
(LASSO)
analyses,
subsequently
validated
its
accuracy
stratifying
according
median
score.
Ultimately,
some
crucial
independent
pinpointed
their
expression,
roles,
characteristics
explored
both
laboratory
live
models.
Results
Findings
revealed
52
differentially
expressed
(DEGs),
21
significantly
outcomes.
These
utilized
categorize
two
subtypes.
Subtype
B
worse
compared
A,
though
subtypes
distinguishable.
enriched
mainly
concentrated
actively
group.
Following
this,
five
genes,
proven
possess
significant
value.
link
identified
between
microenvironment
risk-associated
scores.
IL33
as
an
important
research
Its
vivo
expression
results
aligned
data
findings,
showing
low
BRCA.
Furthermore,
overexpression
inhibited
growth
motility
vitro
,
while
also
enhancing
vulnerability
destruction
activated
CD8
+
T
cells.
Conclusion
ERG-based
effectively
predicts
shows
strong
microenvironment.
stands
out
marker,
onset
advancement
This
highlights
necessity
additional
studies
indicates
that
might
be
potential
target
treatment.
