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.
Cancers,
Год журнала:
2024,
Номер
16(15), С. 2635 - 2635
Опубликована: Июль 24, 2024
HER2
(human
epidermal
growth
factor
receptor
2)
is
highly
expressed
in
a
variety
of
cancers,
including
breast,
lung,
gastric,
and
pancreatic
cancers.
Its
amplification
linked
to
poor
clinical
outcomes.
At
the
genetic
level,
encoded
by
ERBB2
gene
(v-erb-b2
avian
erythroblastic
leukemia
viral
oncogene
homolog
2),
which
frequently
mutated
or
amplified
thus
spurring
extensive
research
into
modulation
inhibition
as
viable
anti-cancer
strategies.
An
impressive
body
FDA-approved
drugs,
anti-HER2
monoclonal
antibodies
(mAbs),
antibody–drug
conjugates
(ADCs),
HER2-tyrosine
kinase
inhibitors
(TKIs),
have
demonstrated
success
enhancing
overall
survival
(OS)
disease
progression-free
(PFS).
Yet,
drug
resistance
remains
persistent
challenge
raises
risks
metastatic
potential
tumor
relapse.
Research
alternative
therapeutic
options
for
HER2+
breast
cancer
therefore
proves
critical
adapting
this
ever-evolving
landscape.
This
review
highlights
current
HER2-targeted
therapies,
discusses
predictive
biomarkers
resistance,
introduces
promising
emergent
therapies—especially
combination
therapies—that
are
aimed
at
overcoming
context
cancer.
Abstract
Tuning
immune‐cold
tumor
hot
has
largely
attracted
attention
to
improve
cancer
treatment,
including
immunotherapy
and
antibody‐drug
conjugates
(ADCs).
Utilizing
multiomic
analyses
experimental
validation,
this
work
identifies
a
pivotal
role
for
the
USP10/B7‐H4
proteolytic
axis
in
mediating
interplay
between
immune
responses
ADC
efficacy,
particularly
sacituzumab
govitecan
(SG)
treating
triple
negative
breast
cancers
(TNBCs).
Mechanistically,
inhibition
of
autocrine
motility
factor
receptor
(AMFR)‐mediated
ubiquitylation
B7‐H4
by
deubiquitinase
USP10
leads
stabilization
B7‐H4,
which
suppresses
activity
reduces
SG
treatment
effectiveness.
Pharmacological
promotes
degradation
enhancing
immunogenicity
consequently
improving
tumor‐killing
efficacy
SG.
In
preclinical
TNBC
models,
suppression
is
effective
increasing
killing
reducing
growth,
especially
tumors
with
high
/B7‐H7
signature.
Collectively,
these
findings
uncover
novel
strategy
targeting
immunosuppressive
molecule
therapy.
Cancers,
Год журнала:
2024,
Номер
16(19), С. 3250 - 3250
Опубликована: Сен. 24, 2024
Triple-negative
breast
cancer
(TNBC)
lacks
the
expression
of
estrogen
receptors
(ERs),
human
epidermal
growth
factor
receptor
2
(HER2),
and
progesterone
(PRs).
TNBC
has
poorest
prognosis
among
subtypes
is
more
likely
to
respond
immunotherapy
due
its
higher
PD-L1
a
greater
percentage
tumor-infiltrating
lymphocytes.
Immunotherapy
revolutionized
treatment,
especially
with
FDA’s
approval
pembrolizumab
(Keytruda)
combined
chemotherapy
for
advanced
cases,
opening
new
avenues
treating
this
deadly
disease.
Although
can
significantly
improve
patient
outcomes
in
subset
patients,
achieving
desired
response
rate
all
remains
an
unmet
clinical
goal.
Strategies
that
enhance
responses
immune
checkpoint
blockade,
including
combining
chemotherapy,
molecularly
targeted
therapy,
or
radiotherapy,
may
rates
outcomes.
In
review,
we
provide
short
background
on
explore
different
types
strategies
are
currently
being
evaluated
TNBC.
Additionally,
review
why
combination
be
beneficial,
overview
strategies,
discuss
novel
immunotherapeutic
opportunities
approved
near
future
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.
