44 | New Scientist | 7 March 2020
evolve immune system resistance can thrive.
“It’s survival of the fittest. It’s not happening
in a jungle or a pond – it’s a prostate or a breast.
But it’s a Darwinian process.”
This knowledge hasn’t yet influenced the
mostly crude and brutal way we treat cancer,
which is sometimes described as slash, burn
and poison, referring to surgery, radiotherapy
and chemotherapy. These approaches can
work if the cancer is caught early enough,
which generally means before it has spread.
But chemotherapy and radiotherapy work by
killing all quickly dividing cells, which means
they also damage the skin, gut and immune
system, causing side effects such as hair loss,
sickness and vulnerability to infections.
More recently, targeted therapies have been
touted as the next big thing. These work by
blocking molecules on cancer cells that are
specific to them, so tend to have fewer side
effects on healthy tissue. This requires testing
someone’s cancer to identify the mutations
involved, so is painted as the ultimate in
personalised medicine.
We often see media coverage when one of
these new treatments reaches the clinic, but
the reality is they usually extend people’s lives
by only a few months. That is because their
developers failed to consider cancer evolution,
says Swanton. A targeted treatment kills all
cancer cells that carry a certain molecule – but
any that don’t have that molecule survive.
It therefore “selects for” growth of cells that
are resistant to it, so within a few months,
tumour cells without that molecule are more
numerous, and the treatment no longer works.
The cancer has developed drug resistance.
Doctors have long been aware that targeted
therapies don’t usually extend people’s lives
for long, but it is only recently that we have
been able to genetically chart how resistanceAn evolution in
cancer treatment
Rapid adaptation has helped cancer resist our best
treatments. Now it may be the key to toppling the
disease. Clare Wilson reports
S
HE doesn’t dwell on it, but 82-year-old
Lydia Knott knows what will happen to
her after death. Her body will be taken
to a laboratory for an unusual post-mortem.
It won’t be to find the cause of her demise.
Knott was diagnosed with lung cancer five
years ago. After surgery to remove part of her
lung, she is now doing well: “Fine for an
82-year-old, I can’t complain.” But if the disease
returns and kills her, Knott wants doctors to
learn more about her cancer through a “warm
autopsy”, so-called because it happens soon
after someone dies.
Within 24 hours, a team would remove up
to 80 tissue samples and preserve them using
liquid nitrogen. One of the aims is to fathom
cancer’s surprising ability to evolve. The same
forces that shape the tree of life also drive
tumours to spawn and spread, generating a
vast genetic diversity of cancer cells within a
single person.
Now, thanks to recent leaps in genetic
sequencing, the hope is that we can trace a
cancer’s evolutionary journey and create
powerful treatments using this information.
“We may actually have the technology to cure
many cancers – we just haven’t been using
the right strategy,” says Robert Gatenby at
the Moffitt Cancer Center in Tampa, Florida.
We might even be able to stop tumours
developing in the first place, but it won’t beeasy. “We are battling natural selection, one
of the fundamental laws of the universe,”
says Charles Swanton at the Francis Crick
Institute in London, co-leader of the study
that Knott has signed up to. “But I think this
is our best shot.”A step ahead
We have known since the 1970s that
tumours arise when a mutation occurs in
one of the genes within a cell that control
its reproduction. Our cells are continually
replicating themselves – even in healthy
tissues – by growing and splitting in two,
to replenish those that have worn out.
This process is controlled by hundreds of
genes so that cells divide at the right place and
time. If a cell has a mutation in one of these
genes – perhaps through exposure to cigarette
smoke or ultraviolet rays or just bad luck – it
may start multiplying faster, its progeny
outcompeting healthy cells.
Even if the immune system attacks these
cancer cells, their ability to evolve may thwart
our body’s attempt to destroy them. There are
parallels between the way predators shape
the evolution of prey populations and how
immune system cells kill the most vulnerable
tumour cells, says Mel Greaves at the Institute
of Cancer Research in London. Cancer cells that >Features