Future Horizons in Lung Cancer
Tumour heterogeneity and the impact on patient care
Dr Nicholas McGranahan - The Francis Crick Institute, London, UK
The focus of my talk will be on intratumour heterogeneity, so diversity within tumours. It has been known for quite some time that no two tumours are identical but what we’re looking at is whether if you look at a single tumour whether you look at different regions of that tumour whether you also identify diversity there and whether that might be one of the key causes of drug resistance.
What cancers are you focussing on?
We’re focussing on lung in particular. So we have a large study called TRACERx which involves tracking non-small cell lung cancer evolution over time where we start with the primary tumours and rather than just take, as I said, just one biopsy we take multiple regions of the tumour and then sequence each one of those to try to understand how the tumour has evolved, so what genetic events occurred early and then what events occurred later on.
What are your findings so far?
One of the things we can do with this is we can try to work out what processes are actually causing the mutations, so if we look at that we can see that smoking in these lung cancers causes the early mutations. So we like to depict the evolution of these tumours as phylogenetic trees and you see that the trunk is primarily caused by smoking induced mutations but then there are also lots of mutations that are very heterogeneous and these are caused by other processes. For instance we see APOBEC enzyme being activated causing lots of the diversity that we’re seeing in these tumours.
What are your aims?
One thing is just to get a better understanding of how lung tumours evolve and also to try to understand what are the events that are occurring very early on which therefore might be more amenable to targeting as well. We’re trying to link this also to immunotherapy approaches and whether the heterogeneity plays a role there in whether the therapy is going to be effective or not. So it’s personalised medicine to the next stage, so not only are we treating the tumour but we’re trying to understand every cell within the tumour so the heterogeneity there as well.
Could this lead to potential new targets for drugs?
Potentially and understanding which drugs will actually work for that patient and what mechanisms of resistance actually arise and why they arise.
What would be your take-home message?
The conclusions really are that heterogeneity is something that we really have to consider and we can’t consider the tumour mass as just a single entity but really there is a lot of diversity there. We need to start taking that into account when treating patients as well.
