Medicinal Research Reviews,
Год журнала:
2017,
Номер
38(1), С. 325 - 376
Опубликована: Сен. 1, 2017
Abstract
To
date,
five
cancer
treatment
modalities
have
been
defined.
The
three
traditional
of
are
surgery,
radiotherapy,
and
conventional
chemotherapy,
the
two
modern
include
molecularly
targeted
therapy
(the
fourth
modality)
immunotherapy
fifth
modality).
cardiotoxicity
associated
with
chemotherapy
radiotherapy
is
well
known.
Similar
adverse
cardiac
events
resurging
modality.
Aside
from
newer
agents,
even
most
newly
developed,
immune‐based
therapeutic
anticancer
modality),
e.g.,
immune
checkpoint
inhibitors
chimeric
antigen
receptor
(CAR)
T‐cell
therapy,
unfortunately
led
to
potentially
lethal
in
patients.
Cardiac
complications
represent
unresolved
life‐threatening
conditions
survivors,
while
effective
clinical
management
remains
quite
challenging.
As
a
consequence,
morbidity
mortality
related
now
threaten
offset
some
favorable
benefits
treatments
cancer‐related
survival,
regardless
oncologic
prognosis.
This
review
focuses
on
identifying
critical
research‐practice
gaps,
addressing
real‐world
challenges
pinpointing
real‐time
insights
general
terms
under
context
induced
by
treatment.
information
ranges
basic
science
field
cardio‐oncology
crosses
interface
between
oncology
onco‐pharmacology.
complexity
ongoing
problem
addressed
at
different
levels.
A
better
understanding
these
gaps
may
advance
research
initiatives
development
mechanism‐based
diagnoses
for
cardiotoxicity.
The
human
genome
encodes
538
protein
kinases
that
transfer
a
γ-phosphate
group
from
ATP
to
serine,
threonine,
or
tyrosine
residues.
Many
of
these
are
associated
with
cancer
initiation
and
progression.
recent
development
small-molecule
kinase
inhibitors
for
the
treatment
diverse
types
has
proven
successful
in
clinical
therapy.
Significantly,
second
most
targeted
drug
targets,
after
G-protein-coupled
receptors.
Since
first
inhibitor,
early
1980s,
37
have
received
FDA
approval
malignancies
such
as
breast
lung
cancer.
Furthermore,
about
150
kinase-targeted
drugs
phase
trials,
many
kinase-specific
preclinical
stage
development.
Nevertheless,
factors
confound
efficacy
molecules.
Specific
tumor
genetics,
microenvironment,
resistance,
pharmacogenomics
determine
how
useful
compound
will
be
given
This
review
provides
an
overview
discovery
relation
oncology
highlights
challenges
future
potential
therapies.
International Journal of Molecular Sciences,
Год журнала:
2014,
Номер
15(8), С. 13768 - 13801
Опубликована: Авг. 8, 2014
Chemotherapeutic
and
cytotoxic
drugs
are
widely
used
in
the
treatment
of
cancer.
In
spite
improvements
life
quality
patients,
their
effectiveness
is
compromised
by
several
disadvantages.
This
represents
a
demand
for
developing
new
effective
strategies
with
focusing
on
tumor
cells
minimum
side
effects.
Targeted
cancer
therapies
personalized
medicine
have
been
defined
as
type
emerging
treatments.
Small
molecule
inhibitors
(SMIs)
among
most
targeted
therapy.
The
growing
number
approved
SMIs
receptor
tyrosine
kinases
(RTKs)
i.e.,
kinase
(TKIs)
clinical
oncology
imply
increasing
attention
application
these
therapeutic
tools.
Most
current
RTK–TKIs
preclinical
settings
multi-targeted
Only
few
specific/selective
developed
patients.
Specific/selective
shown
less
deleterious
effects
compared
to
inhibitors.
review
intends
highlight
importance
TKIs
future
development
more
manageable
agents.
article
provides
an
overview
of:
(1)
characteristics
function
RTKs
TKIs;
(2)
recent
advances
improvement
or
settings;
(3)
TKIs.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Июль 7, 2023
Since
their
invention
in
the
early
2000s,
tyrosine
kinase
inhibitors
(TKIs)
have
gained
prominence
as
most
effective
pathway-directed
anti-cancer
agents.
TKIs
shown
significant
utility
treatment
of
multiple
hematological
malignancies
and
solid
tumors,
including
chronic
myelogenous
leukemia,
non-small
cell
lung
cancers,
gastrointestinal
stromal
HER2-positive
breast
cancers.
Given
widespread
applications,
an
increasing
frequency
TKI-induced
adverse
effects
has
been
reported.
Although
are
known
to
affect
organs
body
lungs,
liver,
tract,
kidneys,
thyroid,
blood,
skin,
cardiac
involvement
accounts
for
some
serious
complications.
The
frequently
reported
cardiovascular
side
range
from
hypertension,
atrial
fibrillation,
reduced
function,
heart
failure
sudden
death.
potential
mechanisms
these
unclear,
leading
critical
knowledge
gaps
development
therapy
guidelines.
There
limited
data
infer
best
clinical
approaches
detection
therapeutic
modulation
effects,
universal
consensus
regarding
various
management
guidelines
is
yet
be
reached.
In
this
state-of-the-art
review,
we
examine
pre-clinical
studies
curate
evidence
on
pathophysiology,
mechanisms,
reactions.
We
expect
that
review
will
provide
researchers
allied
healthcare
providers
with
up-to-date
information
natural
history,
risk
stratification,
emerging
cancer
patients.
Endocrine Related Cancer,
Год журнала:
2016,
Номер
23(4), С. R185 - R205
Опубликована: Апрель 1, 2016
Abstract
Thyroid
cancer
is
rare,
but
it
the
most
frequent
endocrine
malignancy.
Its
prognosis
generally
favorable,
especially
in
cases
of
well-differentiated
thyroid
cancers
(DTCs),
such
as
papillary
and
follicular
cancers,
which
have
survival
rates
approximately
95%
at
40
years.
However,
15–20%
became
radioiodine
refractory
(RAI-R),
until
now,
no
other
treatments
been
effective.
The
same
problems
are
found
poorly
differentiated
(PDTC)
anaplastic
(ATC)
least
30%
medullary
(MTC)
cases,
very
aggressive
not
sensitive
to
radioiodine.
Tyrosine
kinase
inhibitors
(TKIs)
represent
a
new
approach
treatment
advanced
RAI-R
DTC,
MTC,
PDTC,
and,
possibly,
ATC.
In
past
10
years,
several
TKIs
tested
for
advanced,
progressive,
tumors,
some
them
recently
approved
use
clinical
practice:
sorafenib
lenvatinib
DTC
PDTC
vandetanib
cabozantinib
MTC.
objective
this
review
present
current
status
with
innovative
targeted
therapies
by
describing
both
benefits
limits
their
based
on
experiences
reported
so
far.
A
comprehensive
analysis
description
molecular
basis
these
therapies,
well
therapeutic
perspectives,
reported.
Some
practical
suggestions
given
choice
patients
be
treated
management,
particular
regard
potential
side
effects.
Chemical Research in Toxicology,
Год журнала:
2015,
Номер
29(4), С. 473 - 504
Опубликована: Ноя. 20, 2015
Attrition
due
to
nonclinical
safety
represents
a
major
issue
for
the
productivity
of
pharmaceutical
research
and
development
(R&D)
organizations,
especially
during
compound
optimization
stages
drug
discovery
early
clinical
development.
Focusing
on
decreasing
safety-related
attrition
is
not
new
concept,
various
approaches
have
been
experimented
with
over
last
two
decades.
Front-loading
testing
funnels
in
Discovery
vitro
toxicity
assays
designed
rapidly
identify
unfavorable
molecules
was
approach
adopted
by
most
R&D
organizations
few
years
ago.
However,
this
has
also
non-negligible
opportunity
cost.
Hence,
significant
refinements
"fail
early,
fail
often"
paradigm
proposed
recently
reflect
complexity
accurately
categorizing
compounds
data
points
without
taking
into
account
other
important
contextual
aspects,
particular
efficacious
systemic
tissue
exposures.
This
review
provides
an
overview
toxicology
models
that
can
be
used
at
series/lead
identification
lead
guide
inform
chemistry
efforts,
as
well
personal
view
how
best
use
them
meet
objectives
consistent
sustainable
model.
The
scope
limited
small
molecules,
large
are
associated
challenges
quite
different.
Finally,
perspective
several
emerging
technologies
may
impact
evaluation
provided.
