Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Nov. 2, 2023
Abstract
Objective
Hepatocellular
carcinoma
(HCC)
is
an
extremely
deadly
cancer
with
few
effective
therapeutic
options
available.
Ceramide
synthases
(CERS),
a
family
of
enzymes
that
regulate
sphingolipid
metabolism,
have
been
suggested
to
play
role
in
initiation
and
progression.
Whereas
the
specific
functions
CERS
HCC
pathogenesis
not
yet
fully
elucidated.
Methods
The
TCGA
ICGC
databases
were
employed
analyze
expression
levels
clinical
relevance
genes
HCC.
Functional
enrichment
analyses
performed
identify
pathways
associated
CERS5.
correlation
between
CERS5
tumor
immune
microenvironment
was
investigated.
mutation
landscape
immunotherapy
efficacy
evaluated.
experiments
vitro
conducted
assess
CERS5’s
impact
on
cell
proliferation
invasion.
Results
Aberrant
detected
only
but
also
other
cancers,
has
linked
both
overall
survival
disease-free
survival.
Among
members,
identified
as
prognosis-related
gene,
up-regulated
validated
database
tissue
samples.
Higher
poorer
prognosis
well
advanced
pathologic
stage
grade,
confirmed
by
databases.
Besides,
prognostic
nomogram
combining
stage,
status,
established
further
validated,
which
favorable
value
for
prediction.
showed
overexpression
resulted
enriched
carcinogenesis,
drug
PI3K/AKT/mTOR
signaling
pathway,
immune-related
pathways.
In
addition,
correlated
positively
immunogenic
death
modulators
checkpoints,
infiltration,
response,
featured
immunologically
“hot”
environment
microenvironment.
Finally,
functional
knockdown
shown
inhibit
growth
invasion
hepatocellular
carcinoma,
potentially
through
targeting
pathway.
Conclusions
Based
our
findings,
appears
great
potential
precise
biomarker
novel
target
The Oncologist,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 22, 2024
Abstract
Background
Rechallenge
with
immune
checkpoint
inhibitor
(ICI)
seemed
favorable
in
several
tumors,
but
clinical
experience
on
esophageal
squamous
cell
carcinoma
(ESCC)
was
scanty.
This
real-world
study
aimed
to
assess
the
feasibility
and
safety
of
anlotinib
plus
ICI
for
patients
previously
ICI-treated
advanced
ESCC.
Materials
Methods
We
retrospectively
identified
ESCC
who
received
rechallenge
setting
evaluation
outcomes
safety.
Totally
110
ICI-pretreated
patients,
which
89
(80.9%)
prior
first-
or
second-line
treatment,
were
included
from
September
9,
2019,
November
30,
2022.
Most
(63.6%)
discontinued
initial
due
disease
progression.
Results
After
rechallenge,
median
overall
survival
(OS)
progression-free
(PFS)
11.1
(95%
CI,
8.6-13.7)
5.6
4.4-6.8)
months,
respectively;
estimated
OS
PFS
rates
at
12
months
47.6%
36.8%-57.7%)
21.4%
10.9%-34.2%),
respectively.
No
complete
response
reported
21
(19.1%)
attained
partial
response;
objective
rate
19.1%.
Fifty-five
(50.0%)
had
stable
a
control
69.1%.
Of
responders,
duration
6.4
months.
Tendencies
longer
observed
Eastern
Cooperative
Oncology
Group
Performance
0
(P
=
.056).
The
incidence
grade
3
higher
treatment-related
adverse
events
10.0%.
Conclusion
Anlotinib
promising
resulted
encouraging
benefits
Our
findings
provided
preliminary
unique
evidence
help
select
benefiting
this
strategy.
Trial
registration
chictr.org.cn;
number
ChiCTR2300070777
Exploration of Targeted Anti-tumor Therapy,
Journal Year:
2024,
Volume and Issue:
5(6), P. 1271 - 1288
Published: Oct. 18, 2024
Aim:
The
present
study
aims
to
evaluate
the
efficacy
of
rechallenge
with
immune
checkpoint
inhibitors
(ICIs)
compared
chemotherapy
and
predictive
role
clinical
parameters
in
non-small
cell
lung
cancer
(NSCLC)
patients
who
were
rechallenged.
Methods:
included
113
metastatic
NSCLC
had
initially
responded
ICIs
platinum-based
chemotherapy,
either
combination
first
line
or
sequentially
second
line,
but
later
experienced
disease
progression.
Of
those
patients,
52
received
ICI
61
exposed
chemotherapy.
Results:
In
cohort,
median
age
was
67
years,
38
men
(73.1%),
26
(50.0%)
squamous
carcinoma.
Patients
underwent
longer
overall
survival
(OS)
(12.9
months
vs.
9.6
months,
P
=
0.008).
Multivariate
analysis
for
progression-free
(PFS)
OS
revealed
that
poor
Eastern
Cooperative
Oncology
Group
Performance
Status
(ECOG
PS;
PFS:
0.013
OS:
0.037),
absence
objective
response
during
initial
therapy
(PFS:
0.014
0.028),
baseline
neutrophil-to-lymphocyte
ratio
(NLR)
≥
3.8
0.001
0.003)
negative
factors
rechallenge.
three
a
risk
model
named
as
NEO
score,
which
stratified
into
two
groups.
ECOG
PS
0-1,
treatment,
NLR
<
(favorable
group)
PFS
(8.6
3.0
0.001)
(16.6
5.5
all
markers
(poor
group).
There
no
association
between
score
outcomes
did
not
undergo
Conclusions:
showed
benefit,
particularly
3.8,
good
PS,
response.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(23), P. 3996 - 3996
Published: Nov. 28, 2024
Background:
The
persistence
of
chemotherapy-resistant
and
dormant
cancer
cells
remains
a
critical
challenge
in
the
treatment
lung
cancer.
Objectives:
This
review
focuses
on
non-small
cell
small
cancer,
examining
complex
mechanisms
that
drive
resistance.
Methods:
analyzed
current
studies
chemotherapy
resistance
NSCLC
SCLC,
focusing
tumor
microenvironment,
genetic
mutations,
heterogeneity,
emerging
therapies.
Results:
Conventional
targeted
therapies,
such
as
tyrosine
kinase
inhibitors,
often
fail
due
to
factors
including
heterogeneity.
Dormant
cells,
which
can
remain
undetected
quiescent
state
for
extended
periods,
pose
significant
risk
recurrence
upon
reactivation.
These
along
with
intrinsic
mechanisms,
greatly
complicate
efforts.
Understanding
these
pathways
is
crucial
development
more
effective
Emerging
strategies,
combination
therapies
target
multiple
pathways,
are
under
investigation
improve
outcomes.
Innovative
approaches,
antibody–drug
conjugates
protein
degradation,
offer
promising
solutions
by
directly
delivering
cytotoxic
agents
or
degrading
proteins
essential
survival.
organoid
model
shows
substantial
promise
advance
both
research
clinical
applications
this
field,
enhancing
ability
study
develop
personalized
treatments.
integration
underscores
need
continuous
innovation
modalities.
Conclusions:
Personalized
strategies
combine
novel
an
in-depth
understanding
biology
overcome
challenges
posed
treatment-resistant
A
multifaceted
approach
has
potential
significantly
patient
Oncology in Clinical Practice,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 24, 2024
Indications
for
immunotherapy
in
patients
with
non-small-cell
lung
cancer
(NSCLC)
are
expanding,
an
increasing
number
of
receiving
the
perioperative
setting
or
as
consolidation
radiochemotherapy.
Immune
checkpoint
inhibitor
(ICI)-based
regimens
also
being
used
more
and
often
first-line
systemic
setting.
However,
many
cases,
efficacy
is
limited,
it
necessary
to
determine
optimal
sequence
treatment.
There
some
theoretical
rationale
repeated
use
immune
inhibitors,
but
debatable
which
subgroups
likely
benefit
clinically
from
such
Currently,
data
on
retreatment
derived
mainly
retrospective
analyses
reviews
small
treated
clinical
trials,
making
difficult
draw
reliable
conclusions.
a
need
research
identifying
factors
that
will
guide
decision-making,
time
completion
immunotherapy,
initial
response
achieved,
expression
PD-L1,
others.
It
appears
who
discontinued
due
disease
progression
should
not
be
requalified
treatment
currently
available
ICIs.
Treatment
controlled
trials
strategy
cases.
Immunotherapy,
Journal Year:
2024,
Volume and Issue:
16(16-17), P. 1069 - 1078
Published: Sept. 24, 2024
Aim:
Immune-checkpoint
inhibitors
(ICIs)
have
revolutionized
treatment
of
metastatic
head
and
neck
squamous
cell
carcinomas
(HNSCCs).
Our
goal
was
to
assess
for
an
association
between
immune-related
adverse
events
(irAEs)
clinical
outcomes
patients
on
ICIs.
