Archives of Toxicology,
Journal Year:
2021,
Volume and Issue:
95(7), P. 2279 - 2297
Published: May 18, 2021
Over
the
last
decade,
important
clinical
benefits
have
been
achieved
in
cancer
patients
by
using
drug-targeting
strategies.
Nevertheless,
drug
resistance
is
still
a
major
problem
most
therapies.
Epithelial-mesenchymal
plasticity
(EMP)
and
tumour
microenvironment
described
as
limiting
factors
for
effective
treatment
many
types.
Moreover,
epithelial-to-mesenchymal
transition
(EMT)
has
also
associated
with
therapy
different
preclinical
models,
although
limited
evidence
obtained
from
studies
samples.
In
this
review,
we
particularly
deepen
into
mechanisms
of
which
intermediate
epithelial/mesenchymal
(E/M)
states
its
interconnection
to
influence
resistance.
We
describe
how
use
bioinformatics
pharmacogenomics
will
help
figure
out
biological
impact
EMT
on
develop
novel
pharmacological
approaches
future.
Theranostics,
Journal Year:
2020,
Volume and Issue:
10(19), P. 8721 - 8743
Published: Jan. 1, 2020
Over
the
past
few
decades,
substantial
evidence
has
convincingly
revealed
existence
of
cancer
stem
cells
(CSCs)
as
a
minor
subpopulation
in
cancers,
contributing
to
an
aberrantly
high
degree
cellular
heterogeneity
within
tumor.
CSCs
are
functionally
defined
by
their
abilities
self-renewal
and
differentiation,
often
response
cues
from
microenvironment.
Biological
phenotypes
regulated
integrated
transcriptional,
post-transcriptional,
metabolic,
epigenetic
regulatory
networks.
contribute
tumor
progression,
therapeutic
resistance,
disease
recurrence
through
sustained
proliferation,
invasion
into
normal
tissue,
promotion
angiogenesis,
evasion
immune
system,
resistance
conventional
anticancer
therapies.
Therefore,
elucidation
molecular
mechanisms
that
drive
cell
maintenance,
plasticity,
will
enhance
our
ability
improve
effectiveness
targeted
therapies
for
CSCs.
In
this
review,
we
highlight
key
features
regulate
CSC
function
initiation,
therapy
resistance.
We
discuss
factors
such
quiescence,
induction
epithelial-to-mesenchymal
transition
(EMT),
DNA
damage-induced
death.
evaluate
approaches
eliminating
therapy-resistant
subpopulations,
including
drugs
target
signaling
pathways
surface
markers,
viral
therapies,
awakening
quiescent
CSCs,
immunotherapy.
also
assess
impact
new
technologies,
single-cell
sequencing
CRISPR-Cas9
screening,
on
investigation
biological
properties
Moreover,
challenges
remain
be
addressed
coming
years,
experimental
investigating
obstacles
targeting
British Journal of Cancer,
Journal Year:
2021,
Volume and Issue:
125(2), P. 164 - 175
Published: April 6, 2021
Heterogeneity
within
a
tumour
increases
its
ability
to
adapt
constantly
changing
constraints,
but
adversely
affects
patient's
prognosis,
therapy
response
and
clinical
outcome.
Intratumoural
heterogeneity
results
from
combination
of
extrinsic
factors
the
microenvironment
intrinsic
parameters
cancer
cells
themselves,
including
their
genetic,
epigenetic
transcriptomic
traits,
proliferate,
migrate
invade,
stemness
plasticity
attributes.
Cell
constitutes
rapidly
reprogramme
gene
expression
repertoire,
change
behaviour
identities,
microenvironmental
cues.
These
features
also
directly
contribute
are
critical
for
malignant
progression.
In
this
article,
we
use
breast
as
an
example
origins
(in
particular,
mutational
spectrum
clonal
evolution
progressing
tumours)
cell
that
shown
by
undergoing
epithelial-to-mesenchymal
transition),
well
considering
interclonal
cooperativity
sources
heterogeneity.
We
review
current
knowledge
on
functional
contribution
progression,
metastasis
formation
resistance.
Cancer Discovery,
Journal Year:
2021,
Volume and Issue:
11(4), P. 971 - 994
Published: April 1, 2021
Abstract
Metastasis
is
initiated
and
sustained
through
therapy
by
cancer
cells
with
stem-like
immune-evasive
properties,
termed
metastasis-initiating
(MIC).
Recent
progress
suggests
that
MICs
result
from
the
adoption
of
a
normal
regenerative
progenitor
phenotype
malignant
cells,
intrinsic
programs
to
survive
stresses
metastatic
process,
undergo
epithelial–mesenchymal
transitions,
enter
slow-cycling
states
for
dormancy,
evade
immune
surveillance,
establish
supportive
interactions
organ-specific
niches,
co-opt
systemic
factors
growth
recurrence
after
therapy.
Mechanistic
understanding
molecular
mediators
MIC
phenotypes
host
tissue
ecosystems
could
yield
therapeutics
improve
patient
outcomes.
Significance:
Understanding
origins,
traits,
vulnerabilities
capacity
initiate
metastasis
in
distant
organs,
microenvironments
support
ability
these
surveillance
regenerate
tumor,
critical
developing
strategies
prevention
treatment
advanced
cancer.
Leveraging
recent
our
here
we
review
nature
their
offer
perspective
on
how
this
knowledge
informing
innovative
treatments
cancers.
Journal of Cellular Physiology,
Journal Year:
2019,
Volume and Issue:
235(2), P. 790 - 803
Published: July 8, 2019
Abstract
Cancer
stem
cells
(CSCs),
also
known
as
tumor‐initiating
(TICs),
are
elucidated
that
can
perpetuate
themselves
via
autorestoration.
These
highly
resistant
to
current
therapeutic
approaches
and
the
main
reason
for
cancer
recurrence.
Radiotherapy
has
made
a
lot
of
contributions
treatment.
However,
despite
continuous
achievements,
therapy
resistance
tumor
recurrence
still
prevalent
in
most
patients.
This
might
be
partly
related
existence
CSCs.
In
present
study,
recent
advances
investigation
different
biological
properties
CSCs,
such
their
origin,
markers,
characteristics,
targeting
have
been
reviewed.
We
focused
our
discussion
on
radioresistance
adaptive
responses
CSCs
extrinsic
intrinsic
influential
factors.
summary,
we
suggest
prime
target
Signal Transduction and Targeted Therapy,
Journal Year:
2020,
Volume and Issue:
5(1)
Published: Oct. 7, 2020
Abstract
Resistance
to
cancer
therapy
is
a
major
barrier
management.
Conventional
views
have
proposed
that
acquisition
of
resistance
may
result
from
genetic
mutations.
However,
accumulating
evidence
implicates
key
role
non-mutational
mechanisms
underlying
drug
tolerance,
the
latter
which
focus
will
be
discussed
here.
Such
processes
are
largely
driven
by
tumor
cell
plasticity,
renders
cells
insusceptible
drug-targeted
pathway,
thereby
facilitating
survival
and
growth.
The
concept
plasticity
highlights
significance
re-activation
developmental
programs
closely
correlated
with
epithelial–mesenchymal
transition,
properties
stem
cells,
trans-differentiation
potential
during
exposure.
From
observations
in
various
cancers,
this
provides
an
opportunity
for
investigating
nature
anticancer
resistance.
Over
years,
our
understanding
emerging
phenotype
switching
modifying
therapeutic
response
has
considerably
increased.
This
expanded
knowledge
contributes
developing
novel
strategies
or
combination
regimens
using
available
drugs,
likely
improve
patient
outcomes
clinical
practice.
