1 June 2019 | New Scientist | 7Your own animal avatar
Specially created flies, mice and fish are guiding tailored cancer treatments
Personalised medicine
EVERY person’s cancer is different.
While a certain treatment might
see off one person’s breast cancer,
it may fail to work on someone
else’s, and it can be difficult to
know which drugs will be the
best for a specific tumour.
Now doctors are starting to test
out their options on animals that
have been given replicas of an
individual’s cancer – known as
“cancer avatars”.
One method is to generate
Drosophila fruit flies with the
same genetic mutations as a
person’s cancer. These flies are
small and breed fast, so lots of
them can be generated in multiple
rows of test tubes. Robotic
equipment can then screen
the effectiveness of hundreds
of drug combinations on the flies.
This approach was used to
guide the treatment of a man with
terminal colon cancer. He died
after about three years, but this was
probably longer than he would
have lived otherwise, says Ross
Cagan at the Icahn School of
Medicine at Mount Sinai, New York.
The man’s cancer had already
spread around his body and
developed resistance to several
drugs before any fruit fly avatars
were made. Genetic sequencing
revealed his tumour had at least
nine cancerous mutations.
The team genetically engineered
a strain of flies that had all these
mutations in their gut cells – and
then bred over 300,000 of them.
A robotic system was used
to feed the flies and test different
medicines. In this way, the team
screened 121 medicines – including
cancer drugs and treatments
for other conditions – either
singly or in combinations of
up to three.
Several combinations stopped
the flies from dying and slowed
the growth of their gut tumours.
The doctors eventually went for a
cancer drug called trametinib
and an osteoporosis one called
zoledronate, which had the
best combination of effectiveness
and predicted safety.
Animal avatars are needed
because, although we already have
some cancer medicines designed
to combat individual mutations,
we can’t predict how a tumour
with multiple altered geneswill respond, says Cagan.
“We don’t yet know the best
drug combinations for someone
with nine tumour mutations.”
The approach isn’t a cure,
though. The man stopped
responding to this drug
combination after 11 months.
The team sequenced the DNA
of tumour cells in his bloodand couldn’t identify the
mutations that had made the
cancer resistant to the treatment
(Science Advances, doi.org/c58s).
Mouse avatars are more
widely used. These are being
developed at several universities,
and a US firm, Champions
Oncology, already offers this
testing service to people withcancer. When a person has a
tumour removed, a small piece
is sent to the firm, which then
implants cells from it into a small
number of mice. A few months
later, the results from drug testing
in mice are sent back.
Flies, however, are particularly
amenable to robotic screening
methods, and may be preferable
for those concerned about the
ethics of animal research. The
disadvantage is that they are so
different to humans, having an
extremely simple immune
system, for instance.
All the different models have
pros and cons, says Rita Fior of
the Champalimaud Centre for the
Unknown in Lisbon, Portugal, who
is developing zebrafish avatars.
No large-scale trial has yet
shown that any of these
approaches leads to people
living longer than if their doctors
just used their best judgement.
“Our goal is to predict in advance
what’s the best treatment and
get the right drug the first time,”
says Fior. “Then we can stop
experimenting on patients.” ❚The small size of fruit
flies means millions
can fit in a lab at onceSOLVIN^ ZANKL
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/SPLMost people who die from
cancer are killed by cells that
have spread through their body,
but we know relatively little about
how they disperse. Now a team
has genetically sequenced the
secondary tumours of 10 women
who died from breast cancer, and
found that there are usually just
two or three waves of migration
from the original tumour.
Carlos Caldas of the Cancer
Research UK Cambridge Institute
and his colleagues genetically
sequenced samples from an
average of 19 secondary growths
per person. Because all the
tumour cells in a person’s body
descend from a single cell with
cancerous mutations, they wereable to draw a “family tree”
for each woman, showing how
the tumour cells were related,
and revealing how long ago
they split from each other.
“The number of mutations is
effectively a clock,” says Caldas.
The patterns of mutation
suggested that the maximum
number of spreading events
any woman had was three,
while the lowest was one
(Cell Reports, DOI: 10.1016/
j.celrep/2019.04.098).
The finding will help us to
“know our enemy”, says Caldas.
Other teams are developing
ways of catching and removing
cancer cells as they spread
through the blood.How cancer spreads
300,
flies were bred to carry
the genetic mutations
of a man’s colon cancerClare Wilson