Cancer Discovery,
Год журнала:
2019,
Номер
9(11), С. 1493 - 1510
Опубликована: Окт. 14, 2019
Major
advances
in
our
understanding
of
cancer
pathogenesis
and
therapy
have
come
from
efforts
to
catalog
genomic
alterations
cancer.
A
growing
number
large-scale
studies
uncovered
mutations
that
drive
by
perturbing
cotranscriptional
post-transcriptional
regulation
gene
expression.
These
include
affect
each
phase
RNA
processing,
including
splicing,
transport,
editing,
decay
messenger
RNA.
The
discovery
these
events
illuminates
a
novel
therapeutic
vulnerabilities
generated
aberrant
processing
cancer,
several
which
progressed
clinical
development.
SIGNIFICANCE:
There
is
increased
recognition
genetic
affecting
splicing
polyadenylation
are
common
may
generate
opportunities.
Such
occur
within
an
individual
or
factors
themselves,
thereby
influencing
many
downstream
target
genes.
This
review
discusses
the
biological
impact
on
tumorigenesis
approaches
targeting
cells
bearing
mutations.
Cell,
Год журнала:
2018,
Номер
173(2), С. 321 - 337.e10
Опубликована: Апрель 1, 2018
Highlights•Alteration
map
of
10
signaling
pathways
across
9,125
samples
from
33
cancer
types•Reusable,
curated
pathway
templates
that
include
a
catalogue
driver
genes•57%
tumors
have
at
least
one
potentially
actionable
alteration
in
these
pathways•Co-occurrence
alterations
suggests
combination
therapy
opportunitiesSummaryGenetic
control
cell-cycle
progression,
apoptosis,
and
cell
growth
are
common
hallmarks
cancer,
but
the
extent,
mechanisms,
co-occurrence
differ
between
individual
tumor
types.
Using
mutations,
copy-number
changes,
mRNA
expression,
gene
fusions
DNA
methylation
profiled
by
The
Cancer
Genome
Atlas
(TCGA),
we
analyzed
mechanisms
patterns
somatic
ten
canonical
pathways:
cycle,
Hippo,
Myc,
Notch,
Nrf2,
PI-3-Kinase/Akt,
RTK-RAS,
TGFβ
signaling,
p53
β-catenin/Wnt.
We
charted
detailed
landscape
types,
stratified
into
64
subtypes,
identified
mutual
exclusivity.
Eighty-nine
percent
had
pathways,
57%
targetable
currently
available
drugs.
Thirty
multiple
alterations,
indicating
opportunities
for
therapy.Graphical
abstract
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Янв. 6, 2023
Abstract
Recent
advances
in
neoantigen
research
have
accelerated
the
development
and
regulatory
approval
of
tumor
immunotherapies,
including
cancer
vaccines,
adoptive
cell
therapy
antibody-based
therapies,
especially
for
solid
tumors.
Neoantigens
are
newly
formed
antigens
generated
by
cells
as
a
result
various
tumor-specific
alterations,
such
genomic
mutation,
dysregulated
RNA
splicing,
disordered
post-translational
modification,
integrated
viral
open
reading
frames.
recognized
non-self
trigger
an
immune
response
that
is
not
subject
to
central
peripheral
tolerance.
The
quick
identification
prediction
neoantigens
been
made
possible
advanced
next-generation
sequencing
bioinformatic
technologies.
Compared
tumor-associated
antigens,
highly
immunogenic
provide
emerging
targets
personalized
serve
prospective
predictors
survival
prognosis
checkpoint
blockade
responses.
therapies
will
be
aided
understanding
mechanism
underlying
neoantigen-induced
anti-tumor
streamlining
process
neoantigen-based
immunotherapies.
This
review
provides
overview
on
characterization
outlines
clinical
applications
immunotherapeutic
strategies
based
neoantigens.
We
also
explore
their
current
status,
inherent
challenges,
translation
potential.
Cell,
Год журнала:
2018,
Номер
173(2), С. 305 - 320.e10
Опубликована: Апрель 1, 2018
Highlights•An
overview
of
PanCancer
Atlas
analyses
on
oncogenic
molecular
processes•Germline
genome
affects
somatic
genomic
landscape
in
a
pathway-dependent
fashion•Genome
mutations
impact
expression,
signaling,
and
multi-omic
profiles•Mutation
burdens
drivers
influence
immune-cell
composition
microenvironmentSummaryThe
Cancer
Genome
(TCGA)
has
catalyzed
systematic
characterization
diverse
alterations
underlying
human
cancers.
At
this
historic
junction
marking
the
completion
over
11,000
tumors
from
33
cancer
types,
we
present
our
current
understanding
processes
governing
oncogenesis.
We
illustrate
insights
into
through
synthesis
findings
TCGA
project
three
facets
oncogenesis:
(1)
driver
mutations,
germline
pathogenic
variants,
their
interactions
tumor;
(2)
tumor
epigenome
transcriptome
proteome;
(3)
relationship
between
microenvironment,
including
implications
for
drugs
targeting
events
immunotherapies.
These
results
will
anchor
future
rare
common
primary
relapsed
tumors,
cancers
across
ancestry
groups
guide
deployment
clinical
sequencing.Graphical
abstract
Annual Review of Cancer Biology,
Год журнала:
2018,
Номер
3(1), С. 167 - 185
Опубликована: Ноя. 28, 2018
RNA
splicing,
the
enzymatic
process
of
removing
segments
premature
to
produce
mature
RNA,
is
a
key
mediator
proteome
diversity
and
regulator
gene
expression.
Increased
systematic
sequencing
genome
transcriptome
cancers
has
identified
variety
means
by
which
splicing
altered
in
cancer
relative
normal
cells.
These
findings,
combination
with
discovery
recurrent
change-of-function
mutations
factors
cancers,
suggest
that
alterations
are
drivers
tumorigenesis.
Greater
characterization
parallels
increasing
efforts
pharmacologically
perturb
early-phase
clinical
development
small
molecules
disrupt
patients
cancer.
Here
we
review
recent
studies
global
changes
cancer,
regulation
mitogenic
pathways
critical
transformation,
therapeutically
target
