ACS Medicinal Chemistry Letters,
Год журнала:
2024,
Номер
15(12), С. 2074 - 2076
Опубликована: Ноя. 11, 2024
The
rapid
advances
in
cancer
research
have
led
to
novel
therapeutic
approaches
focusing
on
previously
undruggable
targets
and
immune
evasion
mechanisms.
Recent
innovations
exemplify
these
cutting-edge
strategies,
particularly
KRAS-targeting
therapies
using
PROTAC
technology
modulation
address
resistance
cells.
These
developments
present
promising
methods
for
degrading
oncogenic
proteins
enhancing
system
responses,
potentially
transforming
the
treatment
landscape.
This
Patent
Highlight
showcases
breakthroughs,
emphasizing
their
significant
potential
transform
therapy.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Дек. 9, 2024
CD8+
T
cells
are
crucial
cytotoxic
components
of
the
tumor
immune
system.
In
chronic
inflammation,
they
become
low-responsive,
a
state
known
as
cell
exhaustion
(TEX).
The
aim
checkpoint
blockade
is
to
counteract
TEX,
yet
its
dynamics
in
breast
cancer
remain
poorly
understood.
This
review
defines
TEX
and
outlines
features
underlying
mechanisms.
It
also
discusses
primary
mechanisms
cancer,
covering
inhibitory
receptors,
immunosuppressive
cells,
cytokines,
transcriptomic
epigenetic
alterations,
metabolic
reprogramming,
exosome
pathways,
offering
insights
into
potential
immunotherapy
strategies
for
cancer.
Cells,
Год журнала:
2024,
Номер
13(22), С. 1924 - 1924
Опубликована: Ноя. 20, 2024
Identifying
definitive
biomarkers
that
predict
clinical
response
and
resistance
to
immunotherapy
remains
a
critical
challenge.
One
emerging
factor
is
extracellular
acidosis
in
the
tumor
microenvironment
(TME),
which
significantly
impairs
immune
cell
function
contributes
failure.
However,
acidic
conditions
TME
disrupt
interaction
between
cancer
cells,
driving
tumor-infiltrating
T
cells
NK
into
an
inactivated,
anergic
state.
Simultaneously,
promotes
recruitment
activation
of
immunosuppressive
such
as
myeloid-derived
suppressor
regulatory
(Tregs).
Notably,
acidity
enhances
exosome
release
from
Tregs,
further
amplifying
immunosuppression.
Tumor
thus
acts
"protective
shield,"
neutralizing
anti-tumor
responses
transforming
pro-tumor
allies.
Therefore,
targeting
lactate
metabolism
has
emerged
promising
strategy
overcome
this
barrier,
with
approaches
including
buffer
agents
neutralize
pH
inhibitors
block
production
or
transport,
thereby
restoring
efficacy
TME.
Recent
discoveries
have
identified
genes
involved
(pHe)
regulation,
presenting
new
therapeutic
targets.
Moreover,
ongoing
research
aims
elucidate
molecular
mechanisms
acidification
develop
treatments
modulate
levels
enhance
outcomes.
Additionally,
future
studies
are
crucial
validate
safety
pHe-targeted
therapies
patients.
Thus,
review
explores
regulation
pHe
its
potential
role
improving
immunotherapy.
