Future Oncology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 21
Published: Feb. 12, 2025
Triple-negative
breast
cancer
(TNBC)
presents
a
formidable
global
health
challenge,
marked
by
its
aggressive
behavior
and
significant
treatment
resistance.
This
subtype,
devoid
of
estrogen,
progesterone,
HER2
receptors,
largely
relies
on
stem
cells
(BCSCs)
for
progression,
metastasis,
recurrence.
BCSCs,
characterized
their
self-renewal
capacity
resistance
to
conventional
therapies,
exploit
key
surface
markers
critical
signaling
pathways
like
Wnt,
Hedgehog,
Notch,
TGF-β,
PI3K/AKT/mTOR
Hippo-YAP/TAZ
thrive.
Their
adaptability
is
underscored
mechanisms
including
drug
efflux
enhanced
DNA
repair,
contributing
poor
prognosis
high
recurrence
rates.
The
tumor
microenvironment
(TME)
further
facilitates
BCSC
survival
through
complex
interactions
with
stromal
immune
cells.
Emerging
therapeutic
strategies
targeting
BCSCs
-
ranging
from
immunotherapy
nanoparticle-based
delivery
systems
gene-editing
technologies
aim
disrupt
these
resistant
Additionally,
innovative
approaches
focusing
exosome-mediated
metabolic
reprogramming
show
promise
in
overcoming
chemoresistance.
By
elucidating
the
distinct
characteristics
role
TNBC,
researchers
are
paving
way
novel
treatments
that
may
effectively
eradicate
resilient
cells,
mitigate
ultimately
improve
patient
outcomes.
review
highlights
urgent
need
targeted
address
unique
biology
pursuit
more
effective
interventions
TNBC.
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 1, 2025
Small-molecule
targeted
drugs
have
become
the
mainstream
cancer
treatment
due
to
their
specific
therapy.
However,
drug
resistance
inevitably
happens
patients.
Herein,
we
propose
"targeted
conjugate
(TDC)"
concept
design
that
enhance
antitumor
activity,
reduce
toxicity,
and
reverse
resistance.
Upon
this
idea,
compounds
Lapa-603
Lapa-604
were
obtained
by
modifying
Pt(II)
units
with
Lapatinib's
pharmacophore.
Research
has
found
can
potently
inhibit
proliferation
of
tested
cells
multiple
cell
targeting
EGFR
protein
causing
severe
DNA
damage.
More
importantly,
presented
higher
tumor
growth
inhibitory
efficacy
than
Lapatinib,
Cisplatin,
or
physical
mixtures
in
both
MDA-MB-231
BT474
xenograft
models.
Our
research
provided
promise
for
development
novel
based
on
TDC
effectively
overcome
stronger
activity
lower
toxicity
corresponding
combination
Bioinformatics and Biology Insights,
Journal Year:
2025,
Volume and Issue:
19
Published: Jan. 1, 2025
Introduction:
Breast
cancer
(BC)
is
a
heterogeneous
disease
involving
network
of
numerous
extracellular
signal
transduction
pathways.
The
phosphoinositide
3-kinase
(PI3K)/serine/threonine
kinase
(Akt)/mechanistic
target
rapamycin
(mTOR)
pathway
crucial
for
understanding
the
BC
development.
Phosphoinositide
3-kinase,
phosphatase
and
tensin
homolog
(PTEN),
mTOR,
Akt,
3-phosphoinositide-dependent
1
(PDK1),
FoxO1,
glycogen
synthase
3
(GSK-3),
mouse
double
minute
2
(MDM2),
H-Ras,
proapoptotic
B-cell
lymphoma
(BCL-2)
family
protein
(BAD)
proteins
are
key
drivers
this
potential
therapeutic
targets.
Pleurotus
ostreatus
an
edible
mushroom
that
rich
in
flavonoids
phenols
can
serve
as
inhibitors
PI3K/Akt/mTOR
pathway.
Aim:
This
study
evaluated
anticancer
properties
P
through
structure-based
virtual
screening
22
biologically
active
compounds
present
mushroom.
Method:
Model
optimization
was
carried
out
on
PI3K,
PTEN,
PDK1,
GSK-3,
MDM2,
BAD
molecular
docking
compounds/control
binding
pocket
were
simulated
AutoDock
Vina
PyRx.
drug
likeness,
pharmacokinetic,
pharmacodynamic
features
prospective
leads
all
anticipated.
Result:
Several
potent
selected
driver
identified
from
ostreatus.
Ellagic
acid
with
affinities
−8.0,
−8.1,
−8.2,
−6.2,
−7.1
kcal/mol
BAD,
respectively,
had
better
affinity
compared
their
reference
drugs.
Likewise,
apigenin
(−7.8
kcal/mol),
chrysin
quercetin
(−6.4
chlorogenic
(−6.2
kcal/mol)
to
H-Ras
proteins,
respectively.
Conclusion:
acid,
apigenin,
luteolin,
quercetin,
chrysin,
naringenin
phytochemicals
seen
lead
molecules
due
ability
strongly
bind
under
Analogs
these
also
be
designed
Exploration of neuroscience,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 24, 2025
Neurodegenerative
disorders,
including
Alzheimer’s,
Parkinson’s,
Huntington’s,
and
amyotrophic
lateral
sclerosis,
are
among
the
most
significant
health
concerns
worldwide,
characterized
by
neuronal
dysfunction,
oxidative
stress,
neuroinflammation,
protein
misfolding.
Epigallocatechin
gallate,
a
green
tea
polyphenol,
has
been
reported
to
possess
multifaceted
neuroprotective
properties.
It
reduces
stress
through
free
radical
scavenging,
activation
of
antioxidant
enzymes,
stabilization
mitochondrial
function.
also
inhibits
neuroinflammation
modulation
key
signaling
pathways.
suppresses
amyloid-beta
aggregation
in
Alzheimer’s
alpha-synuclein
fibrillation
thus
attenuating
toxic
accumulation.
Its
activity
induction
autophagy
promotion
synaptic
plasticity
supports
survival
However,
low
bioavailability
metabolic
instability
hinder
its
translation
into
clinic.
Strategies
nanoparticle
encapsulation,
structural
modifications,
combination
therapies
being
explored
overcome
these
challenges.
Future
research
could
establish
epigallocatechin
gallate
as
viable
candidate
for
managing
neurodegenerative
disorders.
Cancers,
Journal Year:
2025,
Volume and Issue:
17(8), P. 1323 - 1323
Published: April 15, 2025
Breast
cancer
is
the
most
common
and
deadly
female-specific
malignancy
in
world.
Four
immunohistochemical
subtypes
are
distinguished:
luminal
A,
B,
HER2-positive,
triple-negative.
In
turn,
HER2-positive
subtype
presents
two
variants
depending
on
status
of
hormone
receptors.
The
variant
that
expresses
them
can
benefit
from
both
anti-HER2
anti-hormonal
therapy.
Today,
MCTP
finds
application
maintenance
therapy
after
standard
care
advanced
breast
when
patient’s
clinical
condition
already
seriously
compromised
by
metastatic
disease;
this
context,
it
used
as
a
first-line
treatment,
pre-treated
subjects,
or
rescue
treatment.
Here,
use
adjuvant
oral
surgery
at
an
early
stage
HER-2
hormone-positive
local
proposed,
where
effective
treatment
options
available,
such
(e.g.,
trastuzumab,
pertuzumab),
tamoxifen,
letrozole),
radiotherapy,
and,
case
strong
PD-1
positivity,
immunotherapy.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 28, 2024
SUMMARY
Current
chemotherapies
provide
limited
clinical
benefits
to
patients
with
pancreatic
ductal
adenocarcinoma
(PDAC),
partly
due
the
lack
of
effective
biomarkers
for
personalized
therapy.
KRAS
activating
mutations
occur
in
almost
90%
PDAC
cases,
leading
a
subset
tumors
d
ependent
on
survival
(dKRAS).
Assessing
dKRAS
can
be
achieved
using
gene
expression
signature
scores,
independent
specific
mutations,
allowing
therapies.
Previous
studies
have
shown
that
dKRAS-PDAC
cells
are
more
sensitive
FDA-approved
drug
decitabine
(DEC),
although
mechanism
remains
unclear.
While
DEC
is
approved
hematological
tumors,
its
repurposing
solid
poses
challenges
high-dose
side
effects.
Identifying
optimal
pharmacological
approaches
and
response
crucial
successful
implementation
other
tumors.
Our
investigation
revealed
low-dose
combined
PARP
inhibitor
olaparib
(OLA)
enhances
antitumor
activity
dKRAS-PDAC.
Mechanistically,
induces
DNA
damage
activates
an
ATR/ATM-mediated
(DDR),
PARP1-mediated
repair
playing
role.
Inhibiting
OLA
activity,
even
BRCA1/2
wild-type
homologous
recombination
(HR)-proficient
but
it
ineffective
KRAS-independent
Thus,
transcriptomic-based
dependency
scores
effectively
predict
efficacy
Additionally,
carrying
BRCA2
mutation,
OLA’s
completely
inhibiting
metastasis
growth
compared
single-drug
treatments.
findings
support
further
evaluation
DEC+OLA
combination
therapy
PDAC,
particularly
dKRAS-positive
irrespective
status.
This
approach
extends
benefit
beyond
BRCA
status,
addressing
limitation
targeted
Furthermore,
we
highlight
DDR
as
key
action
DEC,
role
regulation,
underscoring
mode
this
widely
used
anticancer
drug.
