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Systemic therapeutic strategies for GEP-NETS: what can we expect in the future?
[alpha-thalassemia]
Over
the
last
few
years
,
there
have
been
important
advances
in
the
understanding
of
the
molecular
biology
of
neuroendocrine
tumors
(
NETs
)
that
have
already
translated
into
relevant
advances
in
the
clinic
.
Several
studies
have
extensively
assessed
the
mutational
profile
of
NETs
,
and
have
shown
the
key
roles
that
angiogenesis
and
the
PI
3
K
-AKT-mTOR
pathway
play
in
the
pathogenesis
of
these
tumors
.
Recent
data
has
also
revealed
the
potential
relevance
of
transcription
factors
such
as
death
domain-associated
protein
,
x-linked
mental
retardation
,
and
α-thalassemia
syndrome
protein
or
ataxia
telangiectasia
-mutated
in
NETs
of
pancreatic
origin
.
This
fast
progress
is
leading
to
a
rapidly
increasing
number
of
new
agents
being
explored
in
the
field
of
NETs
.
However
,
and
despite
some
unquestionable
success
,
objective
remission
rates
remain
low
,
and
evidence
of
a
substantial
survival
impact
is
lacking
.
Thus
,
there
is
an
important
need
to
improve
our
ability
to
identify
patients
most
likely
to
benefit
from
specific
therapies
,
and
to
incorporate
biomarkers
in
the
management
of
NETs
.
In
addition
,
further
efforts
to
understand
mechanisms
of
escape
and
acquired
resistance
to
the
different
available
agents
is
of
utmost
importance
,
and
will
likely
require
performing
paired
tumor
biopsies
(
prior
and
after
treatment
)
or
sequential
sampling
of
surrogate
tissues
.
Combinations
of
approved
agents
with
new
agents
,
either
in
a
rational
or
biomarker-driven
manner
,
are
certainly
warranted
in
this
field
.
Likewise
,
sequential
strategies
to
modulate
and
compensate
for
escape
phenomenons
are
also
of
great
interest
.
It
should
also
be
noted
,
however
,
that
targeted
agents
are
not
innocuous
and
frequently
yield
toxicities
that
need
to
be
adequately
addressed
by
experienced
specialists
,
particularly
when
drug
combinations
are
considered
.
This
review
summarizes
the
salient
data
on
biomarker
and
new
agent
development
for
the
treatment
of
NETs
.
Diseases
Validation
Diseases presenting
"last few years"
symptom
alpha-thalassemia
coats disease
dracunculiasis
erdheim-chester disease
esophageal carcinoma
krabbe disease
omenn syndrome
primary hyperoxaluria type 1
waldenström macroglobulinemia
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