Chopping kidney cancers down at their trunk could lead to new treatments

Cancer Research UK

A new study has discovered the genetic faults at the core of kidney cancers which could be targeted with new treatments, published in Nature Genetics today.

"This research gives us a fascinating insight into how the evolutionary branching of cancers follows certain paths" - Professor Charles Swanton

Cancer Research UK scientists 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.

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.

Study author Professor Charles Swanton, based at Cancer Research UK’s London Research Institute 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 research was funded by Cancer Research UK through the Catalyst Club – a pioneering venture to raise £10 million for various research projects aimed at realising the benefits of personalised medicine for people with cancer.

ENDS

For media enquiries contact the Cancer Research UK press office on 020 3469 8300 or, out of hours, on 07050 264 059.

References

Gerlinger, M. et al The Genomic architecture and evolution of clear cell renal cell carcinomas defined by multi-region sequencing Nature Genetics (2014) doi:10.1038/ng.2891