A new study has discovered the genetic faults at the core of kidney cancers which could be targeted with new treatments.
Professor Charles Swanton and his colleagues 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. 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.
The study, published in Nature Genetics, found that both between and within patients there are similarities in the evolutionary paths the different tumour branches can take. 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.
BRC-supported Professor Swanton 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”.
To read Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing in full click here.
