Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: A systematic review and updated meta-analysis
Cancer Treatment Reviews,
Год журнала:
2025,
Номер
133, С. 102882 - 102882
Опубликована: Янв. 6, 2025
Язык: Английский
Targeting PCSK9, through an innovative cVLP-based vaccine, enhanced the therapeutic activity of a cVLP-HER2 vaccine in a preclinical model of HER2-positive mammary carcinoma
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 30, 2025
HER2-targeted
therapies
have
revolutionized
the
treatment
of
HER2-positive
breast
cancer
patients,
leading
to
significant
improvements
in
tumor
response
rates
and
survival.
However,
resistance
incomplete
remain
considerable
challenges.
Proprotein
convertase
subtilisin/kexin
type
9
(PCSK9)
inhibition
is
a
novel
therapeutic
strategy
for
management
dyslipidemia
by
enhancing
clearance
low-density
lipoprotein
cholesterol
receptors,
however
recent
evidence
also
shows
links
between
PCSK9
cells.
We
present
an
innovative
immunization
approach
combining
capsid
virus-like
particle
(cVLP)-based
vaccines
against
HER2
PCSK9.
The
activity
combined
vaccine
was
evaluated
female
mice
challenged
with
mammary
carcinoma
Controls
included
untreated
treated
cVLP-PCSK9
cVLP-HER2
as
standalone
therapies.
Antibodies
elicited
vaccinations
were
detected
through
ELISA
immunoassay.
functional
antibodies
tested
3D-soft
agar
assay
on
human
+
trastuzumab
sensitive
resistant
Mice
vaccinated
displayed
regression
from
40th
day
after
cell
challenge
100%
remaining
tumor-free
even
4
months
later.
In
contrast,
83%
alone
experienced
initial
regression,
followed
relapse
60%
subjects.
Untreated
developed
progressive
tumors
within
1–2
injection.
strong
anti-human
antibody
responses
(reaching
mg/ml
range)
comprising
multiple
immunoglobulins
isotypes.
anti-PCSK9
responses,
resulting
marked
reduction
serum
levels.
Although
reduced
when
co-administered
cVLP-HER2,
it
remained
significant.
Moreover,
both
induced
anti-HER2
able
inhibit
3D
growth
BT-474
trastuzumab-resistant
C5
Strikingly,
vaccination
more
effective
than
those
results
indicate
that
adjuvant
vaccine,
its
efficacy
holding
promise
overcoming
challenges
posed
therapy.
Язык: Английский
Antibody-drug conjugates in breast cancer treatment: resistance mechanisms and the role of therapeutic sequencing
Cancer Drug Resistance,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 6, 2025
Antibody-drug
conjugates
(ADCs)
are
a
transformative
approach
in
breast
cancer
therapy,
offering
targeted
treatment
with
reduced
toxicity
by
selectively
delivering
cytotoxic
agents
to
cells.
While
ADCs
like
trastuzumab
emtansine
(T-DM1),
deruxtecan
(T-DXd),
and
sacituzumab
govitecan
have
shown
significant
efficacy,
resistance
mechanisms
such
as
antigen
loss,
impaired
internalization,
efflux
of
payloads
challenge
their
effectiveness.
This
review
discusses
these
explores
advanced
strategies
overcome
them,
including
innovations
linker
chemistry,
multi-antigen
targeting,
biomarker-driven
personalization.
Additionally,
therapeutic
sequencing
-
determining
the
optimal
order
other
treatments
chemotherapy,
endocrine
immunotherapy
is
examined
crucial
maximize
ADC
efficacy
manage
resistance.
Evidence-based
strategies,
particularly
for
human
epidermal
growth
factor
receptor
2
(HER2)-positive
triple-negative
(TNBC),
supported
clinical
trials
demonstrating
benefits
both
early-stage
metastatic
settings.
The
potential
combination
therapies,
immune
checkpoint
inhibitors
(ICIs),
further
highlights
evolving
landscape
treatment.
As
technology
advances,
personalized
approaches
integrating
biomarkers
optimized
protocols
offer
promising
avenues
enhance
outcomes
combat
cancer.
Язык: Английский
Efficacy and safety of pyrotinib in the treatment of HER2-positive liver metastatic advanced breast cancer
Frontiers in Oncology,
Год журнала:
2025,
Номер
15
Опубликована: Апрель 8, 2025
This
study
aimed
to
evaluate
the
efficacy
and
safety
of
pyrotinib
in
treatment
HER2-positive
breast
cancer
patients
with
without
liver
metastasis.
A
retrospective
analysis
was
conducted
on
91
advanced
cancer,
who
were
treated
between
March
2019
April
2022.
The
categorized
into
two
groups
based
presence
or
absence
metastases,
their
overall
survival
(OS),
progression-free
(PFS),
response
compared.
Adverse
effects
analyzed
assess
pyrotinib.
cohort
include
29
metastasis
62
without.
median
significantly
shorter
group
(15.8
months)
than
that
non-liver
(31.4
months,
P
=
0.0036).
statistically
significant
difference
observed
PFS
(8.7
vs.
18.4
(P
0.0272).
Univariate
revealed
younger
age
(<60
years)
<
0.0001),
negative
progesterone
receptor
expression
0.0028),
higher
Ki67
levels
lymph
node
0.0001)
more
likely
benefit
from
treatment.
Comparative
showed
incidence
rates
anemia
(58.6%
40.3%)
elevated
aspartate
transaminase
level
(31.0%
vs
8.1%)
compared
0.05).
Pyrotinib-based
therapy
is
efficacious
safe
for
while
further
large-scale
clinical
trials
are
warranted
validate
these
results.
Язык: Английский
Current progress and remaining challenges of peptide–drug conjugates (PDCs): next generation of antibody-drug conjugates (ADCs)?
Journal of Nanobiotechnology,
Год журнала:
2025,
Номер
23(1)
Опубликована: Апрель 22, 2025
Drug
conjugates
have
emerged
as
a
promising
alternative
delivery
system
designed
to
deliver
an
ultra-toxic
payload
directly
the
target
cancer
cells,
maximizing
therapeutic
efficacy
while
minimizing
toxicity.
Among
these,
antibody-drug
(ADCs)
garnered
significant
attention
from
both
academia
and
industry
due
their
great
potential
for
therapy.
However,
peptide-drug
(PDCs)
offer
several
advantages
over
ADCs,
including
more
accessible
industrial
synthesis,
versatile
functionalization,
high
tissue
penetration,
rapid
clearance
with
low
immunotoxicity.
These
factors
position
PDCs
up-and-coming
drug
candidates
future
Despite
potential,
face
challenges
such
poor
pharmacokinetic
properties
bioactivity,
which
hinder
clinical
development.
How
design
meet
needs
is
big
challenge
urgent
resolve.
In
this
review,
we
first
carefully
analyzed
general
consideration
of
successful
PDC
learning
ADCs.
Then,
summarised
basic
functions
each
component
construct,
comprising
peptides,
linkers
payloads.
The
peptides
in
were
categorized
into
three
types:
tumor
targeting
cell
penetrating
peptide
self-assembling
peptide.
We
then
these
delivery,
overcoming
resistance,
controlling
release
improving
reduced
non-specific
To
better
understand
druggability
PDCs,
discussed
pharmacokinetics
also
briefly
introduced
current
trials.
Lastly,
perspectives
development
oncology
PDC.
This
review
aimed
provide
useful
information
construction
applications.
Язык: Английский
Predictive Factors of Antibody–Drug Conjugate Treatment in Metastatic Breast Cancer: A Narrative Review
Cancers,
Год журнала:
2024,
Номер
16(23), С. 4082 - 4082
Опубликована: Дек. 5, 2024
Antibody-drug
conjugates
(ADCs)
have
revolutionized
the
treatment
landscape
for
metastatic
breast
cancer,
offering
targeted
delivery
of
cytotoxic
agents
with
improved
efficacy
and
tolerability
compared
to
conventional
chemotherapy.
This
narrative
review
explores
key
predictive
factors
influencing
ADCs,
focusing
on
HER2-targeted
therapies,
such
as
trastuzumab
emtansine
deruxtecan,
well
sacituzumab
govitecan
triple-negative
cancer.
HER2
expression,
TROP-2
levels,
hormone
receptor
status,
tumor
microenvironment
emerge
critical
biomarkers
patient
selection
therapeutic
outcomes.
Additionally,
we
discuss
resistance
mechanisms,
antigen
loss,
impaired
drug
internalization,
role
circulating
DNA
in
predicting
ADC
response.
Finally,
future
perspectives
sequential
use
ADCs
potential
combination
therapies
are
highlighted,
along
emerging
targeting
alternative
antigens
like
HER3
LIV-1.
Overall,
identifying
overcoming
mechanisms
essential
optimizing
thereby
improving
Язык: Английский
Unlocking Natural Potential: Antibody‐Drug Conjugates With Naturally Derived Payloads for Cancer Therapy
Phytotherapy Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 17, 2024
ABSTRACT
Natural
compound‐derived
chemotherapies
remain
central
to
cancer
treatment,
however,
they
often
cause
off‐target
side
effects
that
negatively
impact
patients'
quality
of
life.
In
contrast,
antibody‐drug
conjugates
(ADCs)
combine
cytotoxic
payloads
with
antibodies
specifically
target
cells.
Most
approved
and
clinically
investigated
ADCs
utilize
naturally
derived
payloads,
while
those
conventional
synthetic
molecular
limited.
This
review
focuses
on
enhance
the
efficacy
by
linking
them
antibodies.
We
provide
an
overview
core
components
ADCs,
their
working
mechanisms,
FDA‐approved
featuring
such
as
calicheamicin,
camptothecin,
dolastatin
10,
maytansine,
pyrrolbenzodiazepine
(PBD),
immunotoxin
Pseudomonas
exotoxin
A.
also
explores
recent
clinical
advancements
aimed
at
broadening
therapeutic
potential
applicability
in
treating
heterogeneously
composed
tumors
use
beyond
oncology.
Additionally,
this
highlights
are
currently
being
but
have
not
yet
received
approval.
By
summarizing
current
landscape,
provides
insights
into
promising
avenues
for
exploration
contributes
refinement
treatment
protocols
improved
patient
outcomes.
Язык: Английский