Clinical and Translational Medicine,
Год журнала:
2024,
Номер
14(9)
Опубликована: Авг. 29, 2024
Ovarian
cancer
ecosystems
are
exceedingly
complex,
consisting
of
a
high
heterogeneity
cells.
Development
drugs
such
as
poly
ADP-ribose
polymerase
(PARP)
inhibitors,
targeted
therapies
and
immunotherapies
offer
more
options
for
sequential
or
combined
treatments.
Nevertheless,
mortality
in
metastatic
ovarian
patients
remains
because
cells
consistently
develop
resistance
to
single
combination
therapies,
urging
need
treatment
designs
that
target
the
evolvability
The
evolutionary
dynamics
lead
emerge
from
complex
tumour
microenvironment,
heterogeneous
populations,
individual
cell's
plasticity.
We
propose
successful
management
requires
consideration
ecological
disease.
Here,
we
review
current
challenges
discuss
principles
evolution.
conclude
by
proposing
evolutionarily
designed
strategies
cancer,
with
goal
integrating
longitudinal,
quantitative
data
improve
design
drug
resistance.
KEY
POINTS/HIGHLIGHTS:
Tumours
which
non-cancer
interact
evolve
dynamic
ways.
Conventional
inevitably
development
they
fail
consider
tumours'
cellular
Eco-evolutionarily
should
cell
plasticity
patient-specific
characteristics
clinical
outcome
prevent
relapse.
Molecular Informatics,
Год журнала:
2024,
Номер
43(4)
Опубликована: Янв. 23, 2024
De
novo
design
has
been
a
hotly
pursued
topic
for
many
years.
Most
recent
developments
have
involved
the
use
of
deep
learning
methods
generative
molecular
design.
Despite
increasing
levels
algorithmic
sophistication,
molecules
that
are
synthetically
accessible
remains
major
challenge.
Reaction-based
de
takes
conceptually
simpler
approach
and
aims
to
address
synthesisability
directly
by
mimicking
synthetic
chemistry
driving
structural
transformations
known
reactions
applied
in
stepwise
manner.
However,
small
number
hand-coded
restricts
chemical
space
can
be
accessed
there
few
examples
literature
where
their
routes
designed
executed
successfully.
Here
we
describe
application
reaction-based
biologically
active
compounds
as
proof-of-concept
our
reaction
vector-based
software.
Reaction
vectors
derived
automatically
from
allow
access
wide
region
space.
The
was
aimed
at
producing
against
PARP1
which
improved
brain
penetration
properties
compared
existing
inhibitors.
We
synthesised
selection
according
provided
tested
them
experimentally.
results
demonstrate
novel
biological
relevance
also
accessible.
Clinical and Translational Medicine,
Год журнала:
2024,
Номер
14(9)
Опубликована: Авг. 29, 2024
Ovarian
cancer
ecosystems
are
exceedingly
complex,
consisting
of
a
high
heterogeneity
cells.
Development
drugs
such
as
poly
ADP-ribose
polymerase
(PARP)
inhibitors,
targeted
therapies
and
immunotherapies
offer
more
options
for
sequential
or
combined
treatments.
Nevertheless,
mortality
in
metastatic
ovarian
patients
remains
because
cells
consistently
develop
resistance
to
single
combination
therapies,
urging
need
treatment
designs
that
target
the
evolvability
The
evolutionary
dynamics
lead
emerge
from
complex
tumour
microenvironment,
heterogeneous
populations,
individual
cell's
plasticity.
We
propose
successful
management
requires
consideration
ecological
disease.
Here,
we
review
current
challenges
discuss
principles
evolution.
conclude
by
proposing
evolutionarily
designed
strategies
cancer,
with
goal
integrating
longitudinal,
quantitative
data
improve
design
drug
resistance.
KEY
POINTS/HIGHLIGHTS:
Tumours
which
non-cancer
interact
evolve
dynamic
ways.
Conventional
inevitably
development
they
fail
consider
tumours'
cellular
Eco-evolutionarily
should
cell
plasticity
patient-specific
characteristics
clinical
outcome
prevent
relapse.
