Charles Darwin is a father of evolution; describing how from simple beginnings “endless forms most beautiful and most wonderful” arise. But while his theory describes the origin of species; it does not just apply to animals and plants. It is also true of cancer. Like creatures adapting to survive in their environment; cancers are dynamic growing and evolving in response to their unique surroundings; competing to survive.
No one knows this better than our TRACERx team; who are unpicking how lung cancers evolve in unprecedented detail. They’re doing this by following almost 850 patients with the most common type of lung cancer from diagnosis, through treatment and beyond. But they know that zooming in on just the tumor alone is not enough. Charles Swanton is also exploring the environment that each tumor is growing in. And that means paying close attention to one of cancer’s biggest predators, the immune system.
Impact the immune system
What they are really doing is trying to understand what impact the immune system is having on tumor evolution. Nicky McGranahan, a joint lead for the TRACERx team at University College London. And it looks like the approach is paying off. The team has revealed just how big an impact the immune system can have on lung cancer as it develops. Our immune system’s job is to hunt for potential threats, including cancer.
It forms a big part of the tumor’s surroundings; putting pressure on the tumor to adapt to survive. And according to McGranahan, understanding, this environment is critical to cracking tumor evolution. “It’s like Darwin’s finches you can not really understand any evolution without looking at the environment in which that evolution occurs,” he explains. If you stumbled across Darwin’s finches in London’s Natural History Museum, you would see a set of similar, but not identical birds.
You might notice that each bird has a unique beak when judged against others in the line-up. But it would hard to understand the full story behind these birds and their beaks without looking at where they came from. To really appreciate Darwin’s finches; you’d need to take a journey to the Galapagos and get a feel for the different islands and beaches these birds lived on.
Only then could you appreciate how birds living on islands less than 140 miles apart could have evolved such different appearances. It’s only when you look at the whole picture that the story begins to make sense. And that’s what the TRACERx team are doing in lung cancer. For their latest study, the team analyzed samples taken from 88 early-stage lung cancers that hadn’t yet been treated.
The tumor cells’ DNA
As well as looking at changes in the tumor cells’ DNA, they also looked at how much of the genetic code was being read by each tumor cell. When DNA is read, sections of the genetic code are made into a molecule called RNA; which the team tracked and measured. The team now have a much better picture of the intricate relationship between lung cancer and the immune system. And they’ve come away from the exploration with a future direction in mind.
This could be possible for the temporary changes that cancers cells are making to avoid the immune system. But there’s a lot more work to do.”That’s something that we could alter, using treatments. It’s a long way away but at least it suggests that the tumor has taken various steps to evade the immune system, some of which may be targetable.”