Genes & Development,
Год журнала:
2018,
Номер
32(17-18), С. 1141 - 1154
Опубликована: Сен. 1, 2018
Estrogen
receptor
α
(ER)
is
the
major
driver
of
∼75%
breast
cancers,
and
multiple
ER
targeting
drugs
are
routinely
used
clinically
to
treat
patients
with
+
cancer.
However,
many
relapse
on
these
targeted
therapies
ultimately
develop
metastatic
incurable
disease,
understanding
mechanisms
leading
drug
resistance
consequently
utmost
importance.
It
now
clear
that,
in
addition
estrogens,
function
modulated
by
other
steroid
receptors
signaling
pathways
(e.g.,
growth
factor
cytokine
signaling),
affect
patient
outcome.
Here,
we
review
through
which
impact
as
well
discuss
clinical
implications.
Nucleic Acids Research,
Год журнала:
2020,
Номер
48(W1), С. W488 - W493
Опубликована: Март 25, 2020
Abstract
SynergyFinder
(https://synergyfinder.fimm.fi)
is
a
stand-alone
web-application
for
interactive
analysis
and
visualization
of
drug
combination
screening
data.
Since
its
first
release
in
2017,
has
become
widely
used
web-tool
both
the
discovery
novel
synergistic
combinations
pre-clinical
model
systems
(e.g.
cell
lines
or
primary
patient-derived
cells),
better
understanding
mechanisms
treatment
efficacy
resistance.
Here,
we
describe
latest
version
(release
2.0),
which
extensively
been
upgraded
through
addition
features
supporting
especially
higher-order
data
analytics
exploratory
multi-drug
synergy
patterns,
along
with
automated
outlier
detection
procedure,
extended
curve-fitting
functionality
statistical
replicate
measurements.
A
number
additional
improvements
were
also
implemented
based
on
user
requests,
including
new
export
options,
updated
interface,
as
well
enhanced
stability
performance
web-tool.
With
these
improvements,
2.0
expected
to
greatly
extend
potential
applications
various
areas
combinatorial
precision
medicine.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Март 19, 2021
The
majority
of
breast
cancers
express
the
estrogen
receptor
(ERα)
and
agents
targeting
this
pathway
represent
main
treatment
modality.
Endocrine
therapy
has
proven
successful
in
hormone-responsive
cancer
since
its
early
adoption
1940s
as
an
ablative
therapy.
Unfortunately,
therapeutic
resistance
arises,
leading
to
disease
recurrence
relapse.
Recent
studies
increased
our
understanding
how
changes
chromatin
landscape
deregulation
epigenetic
factors
orchestrate
resistant
phenotype.
Here,
we
will
discuss
epigenome
is
integral
determinant
hormone
response
why
are
promising
targets
for
overcoming
clinical
resistance.
Hormones and Cancer,
Год журнала:
2019,
Номер
10(2-3), С. 51 - 63
Опубликована: Фев. 2, 2019
Endometrial
cancer
is
the
most
common
gynecological
in
developed
world,
and
it
one
of
few
types
that
becoming
more
prevalent
leading
to
deaths
USA
each
year.
The
majority
endometrial
tumors
are
considered
be
hormonally
driven,
where
estrogen
signaling
through
receptor
α
(ER)
acts
as
an
oncogenic
signal.
major
risk
factors
some
treatment
options
for
patients
emphasize
a
key
role
disease.
Despite
strong
connections
between
cancer,
important
molecular
aspects
ER
function
remain
poorly
understood;
however,
progress
being
made
our
understanding
cancer.
Here,
we
discuss
evidence
importance
details
cancer-specific
actions
ER,
open
questions
surrounding
Breast Cancer Research,
Год журнала:
2021,
Номер
23(1)
Опубликована: Авг. 15, 2021
In
metastatic
hormone
receptor-positive
breast
cancer,
ESR1
mutations
are
a
common
cause
of
acquired
resistance
to
the
backbone
therapy,
estrogen
deprivation
by
aromatase
inhibition.
How
these
affect
tumor
sensitivity
established
and
novel
therapies
active
areas
research.
These
include
receptor-targeting
agents,
such
as
selective
receptor
modulators,
covalent
antagonists,
degraders
(including
tamoxifen,
fulvestrant,
agents),
combination
therapies,
endocrine
therapy
plus
CDK4/6,
PI3K,
or
mTORC1
this
review,
we
summarize
existing
knowledge
surrounding
mechanisms
action
roles
in
We
then
analyze
recent
literature
on
how
outcomes
therapies.
For
tamoxifen
relative
vitro
but
do
not
clearly
lead
patients,
making
agents
category
promising.
Regarding
nullify
any
inhibitor
component
combination.
Thus,
combinations
using
alternatives
inhibition,
where
non-endocrine
is
efficacious
monotherapy,
still
effective
against
mutations.
results
emphasize
importance
investigating
combinatorial
resistance,
challenging
efforts
are.
also
discuss
future
directions
open
questions,
studying
differences
among
distinct
mutations,
asking
adjust
clinical
decisions
based
molecular
surveillance
testing,
developing
that
Cancer,
Год журнала:
2019,
Номер
125(21), С. 3714 - 3728
Опубликована: Июль 18, 2019
The
acquisition
of
ligand‐independent
ESR1
mutations
during
aromatase
inhibitor
therapy
in
metastatic
estrogen
receptor
(ER)‐positive
breast
cancer
is
a
common
mechanism
hormonal
resistance.
Preclinical
and
clinical
studies
have
demonstrated
that
can
preexist
primary
tumors
be
enriched
metastasis.
Furthermore,
express
unique
transcriptional
profile
favors
tumor
progression,
suggesting
selected
may
influence
Several
groups
used
sensitive
detection
methods
using
patient
liquid
biopsies
to
track
or
truncal
somatic
predict
treatment
outcome
some
these
techniques
eventually
guide
sequential
options
patients.
Further
development
standardization
mutation
tracking
circulating
DNA
ongoing.
Clinically,
patients
with
derive
benefit
when
treated
fulvestrant
CDK4/6‐targeted
therapies,
but
the
more
potent
selective
ER
degraders
and/or
new
targeted
biotherapies
are
needed
overcome
endocrine‐resistant
phenotype
mutant–bearing
tumors.
In
this
review,
we
discuss
mechanisms
resistance
dissemination
as
well
for
tracking,
newly
discovered
potential
therapeutic
targets,
implications
treating
Cancer Discovery,
Год журнала:
2021,
Номер
11(4), С. 874 - 899
Опубликована: Апрель 1, 2021
Resistance
to
anticancer
therapies
includes
primary
resistance,
usually
related
lack
of
target
dependency
or
presence
additional
targets,
and
secondary
mostly
driven
by
adaptation
the
cancer
cell
selection
pressure
treatment.
targeted
therapy
is
frequently
acquired,
on-target,
bypass
alterations,
cellular
plasticity.
immunotherapy
often
primary,
orchestrated
sophisticated
tumor-host-microenvironment
interactions,
but
could
also
occur
after
initial
efficacy,
when
only
partial
responses
are
obtained.
Here,
we
provide
an
overview
resistance
tumor
immune-targeted
discuss
challenges
overcoming
current
future
directions
development.
SIGNIFICANCE:
A
better
earlier
identification
cancer-resistance
mechanisms
avoid
use
ineffective
drugs
in
patients
not
responding
rationale
for
administration
personalized
drug
associations.
clear
description
molecular
interplayers
a
prerequisite
development
novel
dedicated
drugs.
Finally,
implementation
such
immunologic
explorations
prospective
clinical
trials
de-risk
demonstration
more
effective
strategies
randomized
registration
trials,
bring
us
closer
promise
cure.
Frontiers in Endocrinology,
Год журнала:
2019,
Номер
10
Опубликована: Май 24, 2019
The
importance
and
role
of
the
estrogen
receptor
pathway
has
been
well
documented
in
both
breast
cancer
development
progression.
treatment
choice
women
with
metastatic
is
classically
divided
into
a
variety
endocrine
therapies,
3
most
common
being:
selective
modulators,
aromatase
inhibitors
down-regulators.
In
proportion
patients,
resistance
develops
to
therapy
due
sophisticated
at
times
redundant
interference,
molecular
level
between
growth
factor.
progression
considered
be
gradual,
step-wise
process.
Several
mechanisms
have
proposed
but
thus
far
none
them
can
defined
as
complete
explanation
behind
phenomenon
resistance.
Although
multiple
cellular,
immune
are
being
extensively
studied,
their
individual
roles
often
poorly
understood.
this
review,
we
summarize
current
progress
our
understanding
biology
that
predispose
determine
patients.
