7 March 2020 | New Scientist | 47called ulcerative colitis, which puts them
at higher risk of bowel cancer and is also
monitored with regular biopsies. The results,
Graham says, aren’t yet published but are
similar. This same thing may also be the case
for other types of cancer, such as breast and
prostate, says Greaves. In both these tumour
types, we often take biopsies from small lumps
found through screening tests and don’t know
if they are aggressive cancers that must be cut
out straight away or slow-growers suitable for
watchful waiting, sometimes characterised as
“tigers” and “pussycats”.Give us a steer
For decades, scientists have been trying to
develop a test for biopsies to tell us which kind
of cancer someone has. Efforts have focused
on which mutations are present but that hasn’t
led to a useful test so far. We could make more
progress by measuring the cells’ “evolvability”,
says Greaves. That could be influenced by their
genetic diversity, the mutation rate or other
factors yet to be discovered.
This is one of many evolution-based
research programmes planned by the
Institute of Cancer Research. Other avenues
will include developing medicines that slow
down evolution, by reducing the mutation
rate, and a technique known as “evolutionary
steering”. This is still a theoretical concept,
one that designs drugs in such a way that
cells can only develop resistance to them by
mutating in ways that make them susceptible
to other treatments. “We want to assess
candidate drugs by assessing not their ability
to kill cells in a dish, but their ability to restrain
evolution,” says Greaves.
In the US, the National Cancer Institute
began a major new programme focusing
on evolution in 2018, setting up the Arizona
Cancer Evolution Center. Initiatives such as
these will take many years to bear fruit, but
for Greaves, it is the only logical way to tackle
this most fearsome of diseases.
“For decades, we’ve been getting new drugs
by testing them on cells in tissue culture and
it’s not good enough. Every new drug sounds
great, but you still encourage resistance,” he
says. “We need to change track so we see this
as an evolutionary problem. Then, we can try
to find an evolutionary solution.” ❚three months and then immediately switch
to the second. The rationale is that a small
number of resistant cells must have been there
all along, says oncologist Damon Reed, who is
planning the trial. Hitting hard and fast with
the second therapy could have more chance
of killing all the cells.
“The idea is there’s a moment when you
can more likely induce an extinction,” says
Reed. When the number of cells sensitive to
the second therapy are as low as possible,
“that’s your chance to do this”.
Better than improving treatments for cancer
would be stopping it arising in the first place.
This goal is being explored for people who are
at higher risk of certain tumours, again using
evolutionary principles. One such group is
people with Barrett’s oesophagus, a condition
in which the tube going from the mouth to
the stomach becomes inflamed by leaking
stomach acid, making them prone to cancer
of the oesophagus. Those affected have a
check-up every few years with a camera put
down the throat and regular tissue samples
taken to try to spot tumours early. But the
best time to intervene is unclear. Doctors
don’t want to cut out any of the oesophagus
unnecessarily and some people end up getting
cancer despite the screening. Perhaps we can
be more accurate by considering evolution,
says Trevor Graham at the Barts Cancer
Institute in London.
Evolutionary theory says that, all else being
equal, animal or plant species that are more
genetically variable are more likely to branch
into multiple new species under some new
selective pressure, like a change in climate.
In the same way, a genetically diverse group
of cells in the oesophagus may be more likely
to harbour one that can turn cancerous; the
new selective pressure in this case could be
a change in lifestyle, like starting smoking.
Graham’s team put this idea to the test
by sequencing the DNA of cells taken from
routine biopsies of 320 people with Barrett’s
oesophagus. Twenty ended up developing
cancer and those who initially had more
genetically diverse cells in their oesophagus
were more likely to eventually get a tumour.
That means that offering this sequencing
to everyone with the condition might let us
decide whether people are at high risk – and
could have check-ups every few months
instead of years – or low risk. “If someone’s
at very high risk we can keep a close eye on
them, but the real win is to send people home
and tell them not to worry,” says Graham.
His team has now done the same study in
people with an inflammatory bowel conditionClare Wilson
(@ClareWilsonMed) is a
staff writer at New Scientist“ There may
be a better
way to tell if
people have
aggressive or
slow-growing
cancers”
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