bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 5, 2024
Summary
Several
mechanisms
of
resistance
cancer
cells
to
cyclin-dependent
kinase
inhibitors
(CDKi)
have
been
identified,
including
the
upregulation
metabolic
regulators
such
as
glutaminase.
However,
whether
and
targets
are
optimal
has
not
determined.
Here,
we
systematically
analyzed
reprogramming
in
colorectal
exposed
Palbociclib,
a
CDKi
selectively
targeting
CDK4/6,
or
Telaglenestat,
selective
glutaminase
inhibitor.
Through
multiple
approaches,
show
that
Palbociclib
Telaglenestat
elicit
complementary
responses
thus
uniquely
suited
counter
induced
by
reciprocal
drug.
As
such,
while
reduced
tumor
growth
vivo
,
did
significant
effect,
drug
combination
displayed
strong
synergistic
effect
on
growth.
Likewise,
initial
were
followed
signs
adaptation
resistance,
which
prevented
combining
with
Telaglenestat.
In
conclusion,
optimally
forestalls
acquired
cells.
Critical Reviews in Oncology/Hematology,
Год журнала:
2024,
Номер
196, С. 104324 - 104324
Опубликована: Март 8, 2024
Aberrant
cyclin-dependent
kinase
2
(CDK2)
activation
has
been
identified
as
a
main
resistance
mechanism
to
CDK4/6
inhibition
in
hormone-receptor
positive
(HR+)
breast
cancer.
Additionally,
consistent
preclinical
evidence
states
its
crucial
role
MYC
and
CCNE1
overexpressed
cancer
survival,
such
triple-negative
cancers
(TNBC),
thus
representing
an
appealing
relatively
unexplored
target
treatment
opportunity.
Despite
emerging
initial
results
of
novel
CDK2
inhibitors
(CDK2i)
activity,
comprehensive
outcomes
collection
is
currently
absent
from
the
scientific
literature.
We
aim
provide
overview
ongoing
clinical
trials
involving
CDK2i
context
metastatic
(mBC),
either
monotherapy
or
combination
with
other
agents.
The
review
extends
beyond
encompass
CDK4
inhibitors,
combined
CDK2/4/6
well-known
pan-CDK
including
those
specifically
directed
at
CDK2.
Delving
into
results,
we
critically
appraise
observed
efficacy
offer
valuable
insights
their
potential
impact
future
applications.
npj Precision Oncology,
Год журнала:
2023,
Номер
7(1)
Опубликована: Фев. 16, 2023
Endocrine
therapy
(ET)
in
combination
with
CDK4/6
inhibition
is
routinely
used
as
first-line
treatment
for
HR+/HER2-
metastatic
breast
cancer
(MBC)
patients.
However,
30-40%
of
patients
quickly
develop
disease
progression.
In
this
open-label
multicenter
clinical
trial,
we
utilized
a
hypothesis-driven
protein/phosphoprotein-based
approach
to
identify
predictive
markers
response
ET
plus
pre-treatment
tissue
biopsies.
Pathway-centered
signaling
profiles
were
generated
from
microdissected
tumor
epithelia
and
surrounding
stroma/immune
cells
using
the
reverse
phase
protein
microarray.
Phosphorylation
levels
downstream
substrates
Rb
(S780)
FoxM1
(T600)
higher
progressive
(PD)
compared
responders
(p
=
0.02).
Systemic
PI3K/AKT/mTOR
activation
was
detected
PD.
This
not
explained
by
underpinning
genomic
alterations
alone.
As
number
FDA-approved
targeted
compounds
increases,
functional
protein-based
analyses
may
become
critical
component
prediction
selection
MBC
Chitin
and
chitosan-based
bioink
for
3D-printed
flexible
electronics
have
tremendous
potential
innovation
in
healthcare,
agriculture,
the
environment,
industry.
This
biomaterial
is
suitable
3D
printing
because
it
highly
stretchable,
super-flexible,
affordable,
ultrathin,
lightweight.
Owing
to
its
ease
of
use,
on-demand
manufacturing,
accurate
regulated
deposition,
versatility
with
soft
functional
materials,
has
revolutionized
free-form
construction
end-user
customization.
study
examined
employing
chitin
bioinks
build
electronic
devices
optimize
formulation,
parameters,
postprocessing
processes
improve
mechanical
electrical
properties.
The
exploration
bioelectronics
will
open
new
avenues
materials
numerous
industrial
applications.
Diagnostics,
Год журнала:
2023,
Номер
13(5), С. 987 - 987
Опубликована: Март 5, 2023
The
latest
and
newest
discoveries
for
advanced
metastatic
hormone
receptor-positive
(HR+)
human
epidermal
growth
factor
receptor
2-negative
(HER2-)
breast
cancer
are
the
three
cyclin-dependent
kinases
4
6
inhibitors
(CDK4/6i)
in
association
with
endocrine
therapy
(ET).
However,
even
if
this
treatment
revolutionized
world
continued
to
be
first-line
choice
these
patients,
it
also
has
its
limitations,
caused
by
de
novo
or
acquired
drug
resistance
which
leads
inevitable
progression
after
some
time.
Thus,
an
understanding
of
overview
targeted
represents
gold
subtype
is
essential.
full
potential
CDK4/6i
yet
known,
many
trials
ongoing
expand
their
utility
other
subtypes,
such
as
early
cancer,
cancers.
Our
research
establishes
important
idea
that
combined
(CDK4/6i
+
ET)
can
due
therapy,
CDK4/6i,
both.
Individuals’
responses
based
mostly
on
genetic
features
molecular
markers,
well
tumor’s
hallmarks;
therefore,
a
future
perspective
represented
personalized
development
new
biomarkers,
strategies
overcome
combinations
ET
CDK4/6
inhibitors.
aim
our
study
was
centralize
mechanisms
resistance,
we
believe
work
will
have
everyone
medical
field
who
wants
deepen
knowledge
about
resistance.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(9), С. 4862 - 4862
Опубликована: Май 4, 2021
Tumor
dormancy
refers
to
a
critical
stage
of
cancer
development
when
tumor
cells
are
present,
but
does
not
progress.
It
includes
both
the
concept
cellular
dormancy,
indicating
reversible
switch
cell
quiescent
state,
and
that
mass
presence
neoplastic
masses
have
reached
population
equilibrium
via
balanced
growth/apoptosis
rates.
provides
conceptual
framework,
potentially
explaining
major
challenge
in
clinical
oncology,
recurrence,
which
may
occur
years
after
diagnosis.
The
mechanisms
by
tumors
kept
dormant,
what
triggers
their
reawakening,
fundamental
questions
biology.
seems
plethora
intracellular
pathways
extracellular
factors
involved
this
process,
rewiring
plastically
alter
metabolic
proliferative
status.
This
phenomenon
is
highly
dynamic
space
time.
Mechanistic
insights
into
provided
rationale
for
targeting
otherwise
stable
period
development,
order
prevent
recurrence
maximize
therapeutic
benefit.
