Cancer Management and Research,
Journal Year:
2021,
Volume and Issue:
Volume 13, P. 8865 - 8878
Published: Nov. 1, 2021
As
a
key
precancerous
lesion,
colorectal
advanced
adenoma
(CAA)
is
closely
related
to
the
occurrence
and
development
of
cancer
(CRC).
Effective
identification
CAA-related
biomarkers
can
prevent
CRC
morbidity
mortality.
Lipids,
as
an
important
endogenous
substance,
have
been
proved
be
involved
in
CRC.
Lipidomics
technique
that
studies
lipid
metabolism
diseases.
However,
there
are
no
lipidomics
based
on
large
serum
samples
explore
diagnostic
for
CAA.An
integrated
profile
from
50
normal
(NR)
46
CAA
subjects
was
performed
using
ultra-high
performance
liquid
chromatography
tandem
high-resolution
mass
spectrometry
(UHPLC-HRMS).
Lipidomic
data
were
acquired
negative
positive
ionization
modes,
respectively.
Differential
lipids
selected
by
univariate
multivariate
statistics
analyses.
A
receiver
operator
characteristic
curve
(ROC)
analysis
conducted
evaluate
differential
lipids.A
total
53
obtained
combining
statistical
analyses
(P
<
0.05
VIP
>
1).
In
addition,
12
showed
good
(AUC
0.90)
discrimination
NR
operating
analysis.
Of
them,
PC
44:5
35:6e
presented
outstanding
=
1.00,
(95%
CI,
1.00-1.00)).
Moreover,
triglyceride
(TAG)
had
highest
proportion
(37.74%)
major
dysregulated
CAA.This
first
study
profiled
explored
with
ability
contribute
early
prevention
Twelve
effectively
discriminate
between
serve
potential
markers
CAA.
An
obvious
perturbation
TAG
could
formation.
Current Oncology,
Journal Year:
2022,
Volume and Issue:
29(5), P. 3044 - 3060
Published: April 24, 2022
The
discovery
of
immune
checkpoint
proteins
such
as
PD-1/PDL-1
and
CTLA-4
represents
a
significant
breakthrough
in
the
field
cancer
immunotherapy.
Therefore,
humanized
monoclonal
antibodies,
targeting
these
have
been
utilized
successfully
patients
with
metastatic
melanoma,
renal
cell
carcinoma,
head
neck
cancers
non-small
lung
cancer.
US
FDA
has
approved
three
different
categories
inhibitors
(ICIs)
PD-1
(Nivolumab,
Pembrolizumab,
Cemiplimab),
PDL-1
(Atezolimumab,
Durvalumab
Avelumab),
inhibitor
(Ipilimumab).
Unfortunately,
not
all
respond
favourably
to
drugs,
highlighting
role
biomarkers
Tumour
mutation
burden
(TMB),
expression,
microbiome,
hypoxia,
interferon-γ,
ECM
predicting
responses
ICIs-based
current
study
aims
review
literature
updates
on
ICIs
therapy.
JAMA Oncology,
Journal Year:
2023,
Volume and Issue:
9(10), P. 1356 - 1356
Published: Aug. 3, 2023
Only
1
randomized
clinical
trial
has
shown
the
superiority
of
immune
checkpoint
inhibitors
in
patients
with
deficient
mismatch
repair
and/or
microsatellite
instability
(dMMR/MSI)
metastatic
colorectal
cancer
(mCRC)
first-line
setting.To
determine
whether
avelumab
(an
anti-programmed
cell
death
ligand
antibody)
improves
progression-free
survival
(PFS)
compared
standard
second-line
chemotherapy
dMMR/MSI
mCRC.The
SAMCO-PRODIGE
54
is
a
national
open-label
phase
2
that
was
conducted
from
April
24,
2018,
to
29,
2021,
at
49
French
sites.
Patients
mCRC
who
experienced
progression
while
receiving
therapy
were
included
analysis.Patients
receive
or
every
weeks
until
progression,
unacceptable
toxic
effects,
patient
refusal.The
primary
end
point
PFS
according
RECIST
(Response
Evaluation
Criteria
Solid
Tumours),
version
1.1,
evaluated
by
investigators
and
confirmed
dMMR
MSI
status
received
least
dose
treatment
(modified
intention-to-treat
[mITT]
population).A
total
122
enrolled
mITT
population.
Median
age
66
(IQR,
56-76)
years,
65
(53.3%)
women,
100
(82.0%)
had
right-sided
tumor,
52
(42.6%)
BRAF
V600E-mutated
tumors.
There
no
difference
tumor
characteristics
between
groups.
No
new
safety
concerns
either
group
detected,
fewer
treatment-related
adverse
events
grade
3
than
(20
[31.7%]
vs
34
[53.1%];
P
=
.02).
After
median
follow-up
33.3
(95%
CI,
28.3-34.8)
months,
superior
without
targeted
agents
respect
(15
[24.6%]
5
[8.2%]
among
progression;
.03).
Rates
rates
12
months
31.2%
20.1%-42.9%)
19.4%
10.6%-30.2%)
control
groups,
respectively,
27.4%
16.8%-39.0%)
9.1%
3.2%-18.8%)
18
months.
Objective
response
similar
both
groups
(18
[29.5%]
16
[26.2%];
.45).
Among
disease
control,
(75.7%)
9
(19.1%)
ongoing
months.The
showed,
mCRC,
better
duration
over
treatment,
favorable
profile.ClinicalTrials.gov
Identifier:
NCT03186326.
Epigenetics,
Journal Year:
2023,
Volume and Issue:
18(1)
Published: March 12, 2023
N4-acetylcytidine
(ac4C)
is
one
type
of
RNA
modification
found
in
eukaryotes.
acetylation
modifications
are
gradually
expanding
oncology.
However,
the
role
colorectal
cancer
and
its
association
with
microsatellite
status
remain
unclear.
Using
public
databases
vitro
experiments,
we
verified
expression
biological
function
NAT10,
as
key
enzyme,
cancer.
The
results
showed
that
NAT10
was
highly
expressed
cancer,
significantly
promoted
cell
proliferation.
also
involved
several
aspects
homoeostasis
such
ion
transport,
calcium-dependent
phospholipid
binding,
stability.
positively
correlated
immune
infiltration
We
further
constructed
a
risk
regression
model
for
mRNA
using
acetylation-related
differential
genes.
tumour
infiltration,
instability
(MSI)
proportion,
mutation
burden,
patient
response
to
immunotherapy
were
scores.
For
first
time,
our
study
level
elevated
correlates
patients.
Based
on
findings,
may
be
new
target
treatment.
British Journal of Cancer,
Journal Year:
2023,
Volume and Issue:
130(1), P. 143 - 150
Published: Dec. 1, 2023
Abstract
Background
The
immune
response
has
important
clinical
value
in
colorectal
cancer
(CRC)
both
prognosis
and
to
immunotherapy.
This
study
aims
explore
tumour
cell
infiltration
relation
clinically
well-established
molecular
markers
of
CRC.
Methods
Multiplex
immunohistochemistry
multispectral
imaging
was
used
evaluate
cytotoxic
T
cells
(CD8
+
),
Th1
(T-bet
regulatory
(FoxP3
B
(CD20
macrophages
(CD68
)
a
cohort
257
CRC
patients.
Results
We
found
the
expected
association
between
higher
immune-cell
microsatellite
instability.
Also,
whereas
BRAF
-mutated
tumours
displayed
increased
compared
wild-type
tumours,
opposite
seen
for
KRAS
differences
that
were
most
prominent
cells.
opposing
relationships
mutations
with
validated
an
independent
608
A
positive
prognostic
importance
as
well
CRCs
cohorts.
Conclusion
combined
evaluation
MSI
status,
mutational
(cytotoxic
cells)
may
provide
insights
immunotherapy
European Journal of Cancer,
Journal Year:
2024,
Volume and Issue:
202, P. 114033 - 114033
Published: March 21, 2024
One
randomized
phase
III
trial
comparing
chemotherapy
(CT)
with
immune
checkpoint
inhibitors
(ICI)
has
demonstrated
significant
efficacy
of
ICI
in
deficient
DNA
mismatch
repair
system/microsatellite
instability-high
(dMMR/MSI-H)
metastatic
colorectal
cancer.
However,
few
studies
have
compared
CT
other
advanced
dMMR/MSI-H
digestive
tumors.
The EMBO Journal,
Journal Year:
2022,
Volume and Issue:
42(3)
Published: Dec. 21, 2022
Abstract
The
Werner
Syndrome
helicase,
WRN,
is
a
promising
therapeutic
target
in
cancers
with
microsatellite
instability
(MSI).
Long‐term
MSI
leads
to
the
expansion
of
TA
nucleotide
repeats
proposed
form
cruciform
DNA
structures,
which
turn
cause
breaks
and
cell
lethality
upon
WRN
downregulation.
Here
we
employed
biochemical
assays
show
that
helicase
can
efficiently
directly
unfold
thereby
preventing
their
cleavage
by
SLX1‐SLX4
structure‐specific
endonuclease.
are
particularly
prone
explaining
why
these
sequences
preferentially
broken
cells
We
further
demonstrate
activity
mismatch
repair
(MMR)
complexes
MutSα
(MSH2‐MSH6),
MutSβ
(MSH2‐MSH3),
MutLα
(MLH1‐PMS2)
similarly
decreases
level
cruciforms,
although
mechanism
different
from
WRN.
When
combined,
exhibited
higher
than
additive
effects
vitro
processing,
suggesting
MMR
proteins
may
cooperate.
Our
data
explain
how
defects
genome
expanded
repeats,
provide
mechanistic
basis
for
recently
discovered
synthetic‐lethal
interaction
applications
precision
cancer
therapy.
Cells,
Journal Year:
2023,
Volume and Issue:
12(7), P. 1049 - 1049
Published: March 30, 2023
Since
pembrolizumab,
an
anti-programmed
death-1
(PD-1)
antibody,
showed
a
dramatic
response
to
immunogenic
cancers
with
microsatellite
instability-high
(MSI-H)
and/or
deficient
mismatch
repair
(dMMR)
in
the
pilot
clinical
trial
KEYNOTE-016,
subsequent
studies
have
confirmed
durable
responses
of
anti-PD-1
inhibitors
for
MSI-H/dMMR
solid
tumors.
As
immunotherapy
is
described
as
“game
changer,”
therapeutic
landscape
tumors
including
gastrointestinal
has
changed
considerably
last
decade.
An
MSI/MMR
status
been
established
predictive
biomarker
immune
checkpoint
blockades,
playing
indispensable
role
practice
patients
Immunotherapy
also
now
investigated
locally
advanced
cancers.
Despite
this
great
success,
few
populations
do
not
respond
immunotherapy,
possibly
due
existence
intrinsic
or
acquired
resistance
mechanisms.
Clarifying
underlying
mechanisms
remains
future
task,
whereas
attempts
overcome
and
improve
efficacy
are
currently
ongoing.
Herein,
we
review
recent
trials
special
attention
together
basic/translational
findings,
which
provide
their
rationale,
discuss
perspectives
further
development
treatment
field.