Phenotypic
plasticity,
the
capacity
of
cells
to
transition
between
distinct
phenotypic
and
lineage
states
over
time,
is
a
genetically
epigenetically
encoded
trait
essential
for
normal
development
adult
tissue
homeostasis.
In
cancer,
plasticity
programs
can
be
deployed
aberrantly
enable
disease
progression
acquired
therapeutic
resistance.
Cancer
current
barrier
achieving
cures
advanced
cancers
using
available
molecularly
targeted
therapies.
This
review
summarizes
complex
interconnected
molecular
pathways
implicated
in
both
context
homeostasis
cancer.
Molecular
convergent
these
contexts
are
highlighted
while
enabling
distinguished
from
those
that
specify
phenotype
already
plastic
cells.
Key
unresolved
questions
field
discussed
along
with
emerging
technologies
may
used
help
answer
them.
Cancers,
Год журнала:
2025,
Номер
17(5), С. 723 - 723
Опубликована: Фев. 20, 2025
Background/Objectives:
Tumour-associated
macrophages
(TAMs)
are
critical
components
of
the
tumour
microenvironment
(TME),
significantly
influencing
cancer
progression
and
treatment
resistance.
This
review
aims
to
explore
innovative
use
engineered
bacteria
reprogram
TAMs,
enhancing
their
anti-tumour
functions
improving
therapeutic
outcomes.
Methods:
We
conducted
a
systematic
following
predefined
protocol.
Multiple
databases
were
searched
identify
relevant
studies
on
phenotypic
plasticity,
for
reprogramming.
Inclusion
exclusion
criteria
applied
select
studies,
data
extracted
using
standardised
forms.
Data
synthesis
was
performed
summarise
findings,
focusing
mechanisms
benefits
non-pathogenic
modify
TAMs.
Results:
The
summarises
findings
that
can
selectively
target
promoting
shift
from
tumour-promoting
M2
phenotype
tumour-fighting
M1
phenotype.
reprogramming
enhances
pro-inflammatory
responses
activity
within
TME.
Evidence
various
indicates
significant
regression
improved
immune
bacterial
therapy.
Conclusions:
Reprogramming
TAMs
presents
promising
strategy
approach
leverages
natural
targeting
abilities
directly
tumour,
potentially
patient
outcomes
offering
new
insights
into
immune-based
treatments.
Further
research
is
needed
optimise
these
methods
assess
clinical
applicability.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(5), С. 1988 - 1988
Опубликована: Фев. 25, 2025
Colorectal
cancer
(CRC)
is
a
major
cause
of
cancer-related
mortality
worldwide,
with
significant
impact
on
public
health.
Current
treatment
options
include
surgery,
chemotherapy,
radiotherapy,
molecular-targeted
therapy,
and
immunotherapy.
Despite
advancements
in
these
therapeutic
modalities,
resistance
remains
challenge,
often
leading
to
failure,
poor
progression-free
survival,
recurrence.
Mechanisms
CRC
are
multifaceted,
involving
genetic
mutations,
epigenetic
alterations,
tumor
heterogeneity,
the
microenvironment.
Understanding
mechanisms
at
molecular
level
crucial
for
identifying
novel
targets
developing
strategies
overcome
resistance.
This
review
provides
an
overview
diverse
driving
drug
sporadic
discusses
currently
under
investigation
counteract
this
Several
promising
being
explored,
including
targeting
transport,
key
signaling
pathways,
DNA
damage
response,
cell
death
modifications,
stem
cells,
The
integration
emerging
approaches
that
target
aims
enhance
efficacy
current
treatments
improve
patient
outcomes.
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 20, 2025
Abstract
Pancreatic
Ductal
Adenocarcinoma
(PDAC)
remains
a
major
unresolved
disease
because
of
its
remarkable
therapeutic
resistance.
Even
patients
who
respond
to
initial
therapy
experience
relapse
in
most
cases.
The
mechanisms
underlying
therapy-acquired
resistance
supporting
are
poorly
understood.
In
this
study,
we
aimed
determine
the
metabolic
features
PDAC
during
relapse,
specifically
adaptations
mitochondrial
oxidative
metabolism.
We
used
preclinical
mouse
models
(patient-derived
xenografts
and
murine
syngeneic
allografts)
that
present
regression
under
chemotherapeutic
treatment
but
after
certain
time.
Relapsed
tumors
were
analyzed
ex
vivo
by
flow
cytometry
measure
redox
characteristics.
Molecular
investigated
quantification
ATP
antioxidants
levels,
RT-qPCR
bulk
RNA-sequencing.We
show
increased
mass,
superoxide
anions,
total
ROS
relapsed
compared
control
both
models;
membrane
potential
is
model
only.
These
also
observed
treatment-induced
at
onset.
At
molecular
level,
antioxidant
defenses
treatment.
data
suggest
occurring
may
favor
survival
drug-tolerant
persister
(DTP)
cells,
which
persist
subsequent
minimal
residual
responsible
for
cancer
relapse.
Finally,
combined
arsenic
trioxide
(ROS
inducer)
buthionine
sulfoximine
(glutathione
synthesis
inhibitor)
able
completely
prevent
xenografts.
conclusion,
metabolism
vulnerability
pancreatic
DTP
cells
can
be
targeted
Cancer Research,
Год журнала:
2025,
Номер
85(1), С. 7 - 9
Опубликована: Янв. 2, 2025
Therapy-exposed
surviving
cancer
cells
may
have
encountered
profound
epigenetic
remodeling
that
renders
these
drug-tolerant
persisters
candidate
drivers
of
particularly
aggressive
relapses.
Typically
presenting
as
slow-to-nongrowing
cells,
are
senescent
or
senescence-like
cells.
In
this
issue
Cancer
Research,
Ramponi
and
colleagues
study
mTOR/PI3K
inhibitor–induced
embryonic
diapause–like
arrest
(DLA)
a
model
persistence
in
lung
melanoma
compare
persister
condition
with
therapy-induced
senescence
the
same
The
DLA
phenotype
recapitulated
some
but
not
all
features
attributed
to
lacking,
for
instance,
an
inflammatory
secretome
otherwise
known
senescence-associated
secretory
phenotype.
A
CRISPR
dropout
screen
pointed
methyl
group–providing
one-carbon
metabolism
further
H4K20me3-mediated
repression
phenotype–related
IFN
response
genes
selectively
DLA-like
Conversely,
inhibition
H4K20-active
KMT5B/C
methyltransferases
derepressed
programs
was
toxic
These
findings
only
suggest
exploitable
vulnerabilities
also
unveil
general
technical
conceptual
challenges
cultured
multipassage
cell
line–based
studies.
Collectively,
approach
chosen
insights
obtained
will
stimulate
productive
scientific
debate
on
their
reversibility
across
See
related
article
by
et
al.,
p.
32
Cancer Discovery,
Год журнала:
2025,
Номер
15(3), С. 458 - 460
Опубликована: Март 3, 2025
Killarney
and
colleagues
identify
PKN2
as
a
critical
driver
of
mesenchymal
cancer
cell
survival
drug
resistance
through
YAP/TAZ
activation.
Targeting
in
combination
with
first-line
targeted
therapies
offers
potential
strategy
to
eliminate
mesenchymal-like
drug-tolerant
persister
cells.
See
related
article
by
et
al.,
p.
595.
