Understanding mutations could provide cancer clues

This process works like Darwinian evolution, with environmental selection of specific alterations in cells that improve their competitive fitness. ‘The hope is that by changing the environment we will be able to redirect evolution so pre-cancerous cells in normal tissues are selected out and the risks of cancer reduced.’

Phil’s latest research explores mutations and how these can be good for you, and how understanding them could shape future responses to cancer. His research on the skin and on the gullet (oesophagus) has shown that both tissues get taken over by mutant cells as we age. By the age of 70 there are few normal cells left in the oesophagus.

‘As we age our tissues become a Darwinian battleground, with cells carrying different mutations fighting it out. Only the fittest mutants survive’, Phil explains. He adds, ‘Mutations in normal tissues matter, as if cells pick up certain combinations of mutations, they may develop into a cancer. This insight about the huge level of mutations in normal tissues is overturning the way we see the mutations that we find in cancers’. 

‘We now have to explain why cancers are so rare compared with the number of mutant cells in our ageing tissues. One factor that may protect us against cancer is the presence of ‘good’ mutations.  It now seems that there are desirable mutations that may protect us against cancer. We have mutations which protect us against developing tumours alongside the bad mutations which promote cancer in the same tissue. For example, some mutations are able to force microscopic, early tumours out of the oesophagus’.

‘Maybe studying mutations in normal tissues will give us clues into how we can prevent the disease. If we can increase the proportion of anti-cancer mutants and decrease that of pro-cancer mutants in our tissues it may be that the risk of developing cancer can be reduced. Discovering drugs or environmental approaches that do this is what we want to do now’.

Advances in the technologies that enable genes to be sequenced and edited are expediting the work Phil is doing. ‘I don't know whether we'll come up with an intervention that will be suitable for use in people, but we might at least be able to show whether it's possible in a lab model. I think we'll just have to accept that this being taken over by mutations is just part of ageing. However, what we might be able to do is to temper the process, encouraging the good mutations and depleting the bad ones. This may reduce the burden of cancer and possibly other age-related diseases’.