A new study has discovered the genetic faults at the core of
kidney cancers that could be targeted with new
treatments.
Scientists at Cancer Research UK's London Research Institute
(LRI; now part of the Francis Crick Institute) looked at the
complex genetic makeup of tumours from 10 kidney cancer patients
and found there were just two core genetic faults in all the
different samples taken across the tumour.
Crucially, it was these faults that were triggering the very
first stages of kidney cancer development.
Much like a tree, beyond these mutations that form the 'trunk',
numerous branches spread out - all with different genetic faults,
in different parts of the tumour. Almost three-quarters of the many
other genetic faults found are unique to each of the
branches.
But this huge variation in the genetic makeup within the tumour
is not detected when single biopsies are taken - meaning doctors do
not get a true picture of each patient's disease in kidney
cancer.
And this explains why certain targeted treatments are not as
effective as predicted, as they only prune one branch, allowing the
remaining branches to grow into the space
left.
This new study found that both between and within patients there
are similarities in the evolutionary paths the different tumour
branches can take. And importantly, the researchers believe that
this knowledge could be used to predict the genetic routes that
growing tumours will follow - potentially leading to new approaches
that will limit their growth.
Professor Charles Swanton of LRI and the UCL Cancer Institute
said: "This research gives us a fascinating insight into how the
evolutionary branching of cancers follows certain paths. Firstly we
need ways to target the faults that are at the cancer's
trunk.
"Understanding the pre-determined evolutionary routes through
which cancer progresses could mean that we can stay one step ahead
of the disease for each of our patients. And that means future
treatment could be developed to nip this evolutionary force in the
bud."
Professor Nic Jones, Cancer Research UK's chief scientist, said:
"Mapping the genetic differences within tumours is changing the
face of cancer research - revealing the true complexity of the
disease.
"But the good news is that research like this is revealing how
there may be some order and logic to the complexity that could be
exploited with new treatments."
The paper, The Genomic architecture and evolution of clear cell renal cell
carcinomas defined by multi-region sequencing, is published inNature Genetics.