Dr Peter Campbell, Wellcome Trust Sanger Institute
Kat - But now it’s time to delve a bit deeper into cancer genomes. At the Wellcome Trust Sanger Institute, Dr Peter Campbell is joint head of the Cancer Genome Project - an ambitious research programme aimed at analysing the genetic code in thousands of different tumours from patients around the world. I started by asking him what kind of gene changes were involved in cancer and where they come from.
Peter - Most of the gene changes that we’re talking about that drive cancer accumulate during your life as you go through life basically. As we’re walking around, we’re exposed to things that are damaging our DNA. Cigarette smoke is a classic example. Sunlight is another example, and there are also processes that can happen within cells that mean that they can accumulate these genetic changes.
Kat - I remember hearing that just being alive and breathing oxygen is probably more damaging to your DNA than anything else.
Peter - I don't know about [more] than anything else, but it is true that these mutations occur pretty much throughout our life in some or other cells in our body, and if we lived long enough and didn’t die of other things, then it would be statistically inevitable if we would eventually develop cancer, every one of us.
Kat - So, what are you trying to do with the cancer genome project to understand some of these gene faults that are involved in cancer?
Peter - The really exciting thing is that these genetic faults, these mutations that can cause cancer, they tend to be recurrent. So, if you sequence for example, some leukaemias, you will find that the same genetic changes will be found in multiple people, and those genetic changes are the ones that are driving the leukaemia. And that then acts as a natural target for diagnosis. We can use those genetic changes to diagnose someone’s cancer accurately and also for therapy so that we can design treatments that specifically block the action of those drugs. What we’re trying to do here at the cancer genome project is to – to do this is to characterise all of the genes involved in cancer in a systematic way. We take hundreds and thousands of patients with cancer and we sequence the entire genome of their cancers. And then by looking across different patients, we can look at those genes which are most frequently involved in a given cancer type, and then that’s how we set up the targets for future diagnostics and treatment.
Kat - When you look at a cancer cell, often, its DNA is pretty messed up. There's a lot of things that are wrong with it, bits of DNA are stuck to other bits of DNA. There's all sorts of gene faults. How do you tell what's an important gene fault in a cancer cell and what's just there for the ride?
Peter - It’s absolutely true. Cancers can have tens of thousands of genetic changes and mutations, and probably, actually only 10, 20, maybe a few more are actually responsible for turning that cell into a cancer cell. And the way that we identify those 10 or 20 amongst this morass of other things is to look across different patients. So, if we sequence enough different patients, the same genes keep cropping up as recurrently mutated, and that tells us that they're important for those particular cancers.
Kat - You talk about thousands of patients. This is only something that’s been possible, thanks to recent advances in technology. How long now does it take to sequence a tumour genome?
Peter - When we started in the original human genome project which completed about 10 years ago, it took a number of institutes around the world about 10 years and many millions of pounds to sequence the original human genome. Now, we can do an entire cancer genome, plus the normal genome from that same person in about a week for £10,000. In the future, it’s likely that we’ll be doing this for less than a thousand pounds and in even shorter time than a week. So, the change has been absolutely remarkable. The really exciting thing is, that from a scientist’s point of view, this is leading to all sorts of new and exciting insights into the way that cancers develop, and it’s extraordinary time to be doing this kind of research.
Kat - Looking at some of the results that you have already for the cancer genome project, how many cancer genomes have you already looked at and has there been anything intriguing, surprising? What sort of things have you found so far?
Peter - I guess overall, with the latest sequencing technology, we have looked at, I guess several hundred patients with cancer. The kinds of things that we’re finding are remarkable. We’re finding all sorts of new cancer genes, so these are genes that are clearly driving some cancers. Some of them, we had no clue before that they were even remotely involved in cancer, and yet suddenly, these mutations crop up and then we’ve identified a whole new pathway that we can begin to think about – developing drugs to target. We’ve also found some remarkable processes that are actually causing these mutations in the cancers, so not just the genes which are being targeted by the mutations, but actually, what's causing the mutations in the first place. These are really remarkable. I mean, I think rather naively, going into this kind of study expected it to be rather consistent across patients, but it in fact is completely complex. There are all sorts of different processes going on in a number of different cancers. You can tell what a breast cancer will look like and it can look quite different to say a pancreatic cancer and have completely different patterns of mutations. And that’s telling us something about how these genetic changes are occurring and that’s just as remarkable as the discovery of new cancer genes in terms of the sort of scientific value.
Kat - Finding out all these things about cancer genomes, about how complex they are, about all the different faults and mutations, and different ways they can get messed up, does it make you feel optimistic or slightly pessimistic about whether we will beat cancer in the future?
Peter - I think beating cancer is an unattainable goal for all cancers in everybody. I don’t think cancer will ever be cured for every patient that develops it. What I think we will find is that we’ll continue to make iterative progress, so we will develop drugs that have more effectiveness. There’ll be a fraction of patients who benefit tremendously from those patients. There will be more cures, but cancer will always be a devastating diagnosis to receive. It will always be quite challenging to treat, but when I hope is that in more patients, as we go forward, we understand their cancers better, and we can get treatments that are both better tolerated and/or effective, and we build momentum towards improving the lives of people with cancer.
Kat - That was Peter Campbell from the Wellcome Trust Sanger Institute.