Trends in Cell Biology,
Journal Year:
2023,
Volume and Issue:
33(11), P. 903 - 912
Published: May 15, 2023
Evolutionary
cell
biology
explores
the
origins,
principles,
and
core
functions
of
cellular
features
regulatory
networks
through
lens
evolution.
This
emerging
field
relies
heavily
on
comparative
experiments
genomic
analyses
that
focus
exclusively
extant
diversity
historical
events,
providing
limited
opportunities
for
experimental
validation.
In
this
opinion
article,
we
explore
potential
laboratory
evolution
to
augment
evolutionary
toolbox,
drawing
inspiration
from
recent
studies
combine
with
biological
assays.
Primarily
focusing
approaches
single
cells,
provide
a
generalizable
template
adapting
protocols
fresh
insight
into
long-standing
questions
in
biology.
Nature Genetics,
Journal Year:
2024,
Volume and Issue:
56(5), P. 900 - 912
Published: Feb. 22, 2024
Whole
chromosome
and
arm-level
copy
number
alterations
occur
at
high
frequencies
in
tumors,
but
their
selective
advantages,
if
any,
are
poorly
understood.
Here,
utilizing
unbiased
whole
genetic
screens
combined
with
vitro
evolution
to
generate
arm-
subarm-level
events,
we
iteratively
selected
the
fittest
karyotypes
from
aneuploidized
human
renal
mammary
epithelial
cells.
Proliferation-based
karyotype
selection
these
lines
modeled
tissue-specific
tumor
aneuploidy
patterns
patient
cohorts
absence
of
driver
mutations.
Hi-C-based
translocation
mapping
revealed
that
events
usually
emerged
multiples
two
via
centromeric
translocations
occurred
more
frequently
tetraploids
than
diploids,
contributing
increased
diversity
evolving
tetraploid
populations.
Isogenic
clonal
lineages
enabled
elucidation
pro-tumorigenic
mechanisms
associated
common
alterations,
revealing
Notch
signaling
potentiation
as
a
1q
gain
breast
cancer.
We
propose
intrinsic,
proliferative
effects
underlie
Annals of Oncology,
Journal Year:
2023,
Volume and Issue:
34(10), P. 867 - 884
Published: Sept. 28, 2023
Cancer
research
has
traditionally
focused
on
developing
new
agents,
but
an
underexplored
question
is
that
of
the
dose
and
frequency
existing
drugs.
Based
modus
operandi
established
in
early
days
chemotherapies,
most
drugs
are
administered
according
to
predetermined
schedules
seek
deliver
maximum
tolerated
only
adjusted
for
toxicity.
However,
we
believe
complex,
evolving
nature
cancer
requires
a
more
dynamic
personalized
approach.
Chronicling
milestones
field,
show
impact
schedule
choice
crucially
depends
processes
driving
treatment
response
failure.
As
such,
heterogeneity
evolution
dictate
one-size-fits-all
solution
unlikely-instead,
each
patient
should
be
mapped
strategy
best
matches
their
current
disease
characteristics
objectives
(i.e.
'tumorscape').
To
achieve
this
level
personalization,
need
mathematical
modeling.
In
perspective,
propose
five-step
'Adaptive
Dosing
Adjusted
Personalized
Tumorscapes
(ADAPT)'
paradigm
integrate
data
understanding
across
scales
derive
schedules.
We
conclude
with
promising
examples
model-guided
personalization
call
action
address
key
outstanding
challenges
surrounding
collection,
model
development,
integration.
Cell Death and Differentiation,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 20, 2024
Abstract
Genomic
instability,
a
hallmark
of
cancer,
is
direct
consequence
the
inactivation
tumor
suppressor
protein
p53.
Genetically
modified
mouse
models
and
human
samples
have
revealed
that
p53
loss
results
in
extensive
chromosomal
abnormalities,
from
copy
number
alterations
to
structural
rearrangements.
In
this
perspective
article
we
explore
multifaceted
relationship
between
p53,
genomic
stability,
epigenetic
control,
highlighting
its
significance
cancer
biology.
emerges
as
critical
regulator
DNA
repair
mechanisms,
influencing
key
components
pathways
directly
participating
processes.
role
integrity
however
extends
beyond
canonical
functions.
influences
also
landscape,
where
it
modulates
methylation
histone
modifications.
This
control
impacts
expression
genes
involved
suppression
oncogenesis.
Notably,
ability
ensure
cellular
response
demethylation
contributes
maintenance
stability
by
preventing
unscheduled
transcription
repetitive
non-coding
regions.
latter
indicates
causative
p53-mediated
suppression.
Understanding
these
mechanisms
offers
promising
avenues
for
innovative
therapeutic
strategies
targeting
dysregulation
emphasizes
need
further
research
unravel
complexities
relationship.
Ultimately,
insights
hold
potential
transform
treatment
prevention
strategies.
Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(4), P. 113988 - 113988
Published: March 22, 2024
The
basal
breast
cancer
subtype
is
enriched
for
triple-negative
(TNBC)
and
displays
consistent
large
chromosomal
deletions.
Here,
we
characterize
evolution
maintenance
of
chromosome
4p
(chr4p)
loss
in
cancer.
Analysis
Cancer
Genome
Atlas
data
shows
recurrent
deletion
chr4p
Phylogenetic
analysis
a
panel
23
primary
tumor/patient-derived
xenograft
cancers
reveals
early
deletion.
Mechanistically
show
that
associated
with
enhanced
proliferation.
Gene
function
studies
identify
an
unknown
gene,
C4orf19,
within
chr4p,
which
suppresses
proliferation
when
overexpressed—a
member
the
PDCD10-GCKIII
kinase
module
name
PGCKA1.
Genome-wide
pooled
overexpression
screens
using
barcoded
library
human
open
reading
frames
regions,
including
suppress
overexpressed
context-dependent
manner,
implicating
network
interactions.
Together,
these
results
shed
light
on
emergence
complex
aneuploid
karyotypes
involving
adaptive
landscapes
shaping
genomes.
Cancer Cell,
Journal Year:
2025,
Volume and Issue:
43(3), P. 380 - 397.e7
Published: March 1, 2025
Cancer
development
involves
the
co-evolution
of
cancer
cells
and
their
surrounding
microenvironment,
yet
dynamics
this
interaction
within
physical
architecture
remains
poorly
understood.
Here,
we
present
a
spatial
transcriptomic
map
at
single-cell
resolution,
encompassing
127
multi-stage
fields
view
from
43
patients,
to
chart
evolutionary
trajectories
human
esophageal
squamous
cell
carcinoma
(ESCC).
By
analyzing
6.4
million
cells,
reveal
that
ESCC
progression
is
driven
by
proliferative
epithelial
subpopulation
acquires
dedifferentiated
invasive
characteristics.
At
late
precancerous
stage,
these
disrupt
epithelial-stromal
interface
recruit
normal
fibroblasts
via
JAG1-NOTCH1
signaling,
transforming
them
into
cancer-associated
(CAFs).
This
leads
formation
"CAF-Epi"
(CAF
cell)
niche
tumor
edge
shields
immune
surveillance.
The
CAF-Epi
key
indicator
in
other
carcinomas
patient
outcomes.
