NCRI Conference 2013 special edition
Kat: This is the Cancer Research UK podcast NCRI Cancer Conference 2013 special edition – bringing you highlights from the UK’s largest meeting of cancer scientists, doctors, nurses and patient groups, plus a discussion about developing targeted treatments for cancer.
Hello and welcome, I’m Dr Kat Arney. Earlier this month thousands of people descended on Liverpool for the UK’s largest meeting dedicated to cancer research – the NCRI Cancer Conference. Now in its 9th year, the conference is an opportunity to catch up on the very latest advances in research from scientists and doctors here in the UK and beyond. I spoke to our senior science communications officer Sarah Hazell and senior health information manager Jess Kirby to get their impressions of the conference – something that Sarah experienced for the first time.
Sarah: This was my maiden voyage to the NCRI conference and it was a really good gathering of the top guys in the field all coming together to talk about what’s new and what’s happening, to discuss the pros and cons of certain areas, which was really interesting, and also to hear about what we can do in terms of prevention. A whole array of things – opportunities for students to present their work, there was such an array of things on offer so it was a really excellent conference.
Kat: Jess – as an NCRI veteran, what were your impressions of the conference this year?
Jess: I thought there were many really exciting things that happened this year that I hadn’t seen before – loads of exciting progress that we’ve seen in the last year, loads of exciting developments. Some really punchy new data, and some things we’re just still not getting to where we want to and opening up that challenge for researchers to develop those fields in future. So, a great conference.
Kat: And for you, Sarah, what was the most interesting session or talk you went to?
Sarah: For me the most interesting session was the one about cell migration. It’s of major importance because the spread of cancer cells is what kills most patients, so we really don’t know that much about it actually. We had three very good speakers all talking about what was new in that field and how cells physically squeeze their way through tumours, how they bypass different physical things that block their way. It was awesome. In particular they started talking about what their postdocs and students were doing to create ‘assault courses’ for cancer cells to get over hurdles, around corners, through sticky situations – it was a really excellent session and they’re making really good progress in that area.
Kat: How about you, Jess – what were the stand-out sessions this year?
Jess: I think the session that really got my ‘brain juices’ flowing was one about our gut bacteria, and how they might affect our risk of bowel cancer, among other things. You’re made up of more bacterial cells – about ten times more, in fact – than you are of human cells, and we just don’t really understand the wide-ranging effects that these bacteria can have on your health, on your cancer risk. And one of the most interesting experiments in this area was they took some South Africans and some African Americans and completely swapped their diet for two whole weeks, and at the end of that [time] they noticed that the Africa diet, which had been quite good for diversity of your gut bacteria and led you to have quite low cell proliferation rates in the gut, that was completely swapped over when moving to the American diet. Just for two weeks they saw the diversity of their gut bacteria completely change and suddenly all these markers of cell growth started happening. And we wonder if this might help explain some of the effects that we see of diet on bowel cancer risk.
Kat: So it’s definitely one to watch, maybe next year?
Jess: I’m really excited to see how this research field develops, because it’s something that people haven’t really put too much consideration into before. But we’re starting to understand the effects that it has, and really it’s essentially like another organ in your body that we’ve only just found out about.
Kat: And the NCRI conference is a really great opportunity for us to brush up on our knowledge, get the latest results. In your area, what were the really hot results in your area of health information?
Jess: There were two really exciting new studies that are coming out recently about cervical screening – one showing that by switching to HPV testing instead of the cytology tests that we currently use, we could prevent many more cervical cancers from developing than if we just continued using the test. It’s a very good test but this new HPV test could be even better and even more effective, which is very exciting. And secondly, a study looking at the effect of changing the screening age from 20 to 25, the age at which you start screening, that it. This study has compared England, where screening started from the age of 25, to Wales where it started from the age of 20, and found that the harms of screening in that age group would outweigh the benefit. A few cancers would be prevented by screening from the age of 20, but a lot of women would have unnecessary tests and treatments that can lead them to have fairly serious side effects later on in life, so it’s really important to try and get that balance right. This study was a nice validation that starting to screen from the age of 25 is not just a cost-cutting exercise, but that it was really justified from a health perspective as well.
Kat: And for you, Sarah, what are you going to be following up over the next few weeks? What’s really got your ‘brain juices’ going?
Sarah: I’m really interested to hear how they go down this route of personalised medicines and overcoming the major issues that were discussed at the conference in terms of resistance to those treatments. So we heard from a great number of speakers – and there was a particularly good debate about this issue as well – about how they’re going to tackle the issue by maybe making the treatments hit harder, or maybe combining different treatments to make them more effective. So that’s a really exciting area and one to keep an eye on for sure.
Kat: And one of the talks that really stood out for me was Professor Sir Bruce Ponder’s talk, basically going over his life and his career in genetics research into cancer genes. How was that for you?
Sarah: Such an excellent talk! It was so engaging, you could tell that the whole audience in the auditorium were so engrossed with every word that he said. What an incredible man to have achieved so much, and yet to have come from a career where he was trying to be guided down a path that wasn’t anything to do with cancer research, to be pushed down the medical student route. And he stuck to his guns and he completely went the way he wanted to go, and look what he’s achieved – going for lunch with Sir Francis Crick on a weekly basis, investigating the BRCA genes involved in breast cancer. And he’s still going strong, he’s coming up with new findings all the time – he’s just an incredible person.
Kat: It was fantastic to look back as he retires as director of our Cambridge Research Institute, Jess – you were there too, what did you think?
Jess: I was totally inspired by his talk. I think one of the things that really stuck out for me was him saying “you have to follow your dreams and your passions”. He’s got to the stage now where he’s saying, “I might just put my feet up and go fishing or do whatever I want, but I’d be bored in five minute, because I love what I do.” And if I can get to that stage in my career I can say I love what I do and I don’t want to stop, I will be very happy indeed.
Kat: That was Jess Kirby and Sarah Hazell. As Sarah mentioned, one of the most interesting sessions at the meeting was a debate between four of the UK’s leading cancer scientists, asking whether the main priority for cancer research should be developing drugs specifically targeted towards faulty genes within cancer cells. I spoke to two of the debaters – Professor Gerard Evan from Cambridge University and Professor Charlie Swanton from our London Research Institute, to find out more about what was said. I started by asking Gerard why he had proposed the idea of this debate in the first place.
Gerard: Well, I think that there are many discussions that need to be had at the moment. We know so much about cancer but there’s still so much to discover. There’s a limited amount of money available for funding research into it, and it’s really a question of addressing not should we only be not doing certain things and only doing other things, but really where the priorities are. If we want to do the best we can for cancer patients in the near future as well as the long-term future, should we be focusing our energies in one place or another? And this debate was designed to get out the idea that we need to have a discussion about whether we should be focusing on targeted cancer therapies, which have changed the face of cancer treatment over the last ten years, but we don’t quite know where they’re going in the future.
Kat: So you led one side of the debate, which was for it, and Charlie – you were most strongly against it! What was the summary of your argument?
Charlie: The summary of the argument is that in the clinical setting, targeted therapies came into clinical practice with much hype and hope, and I guess rather sceptically what James Larkin and I would say on reflection they perhaps haven’t delivered up to their promise in terms of achieving what we hoped ten years ago would be cures in the metastatic setting. We’re really not seeing that – we’re seeing prolongation of what’s called ‘progression free survival’, but very few examples where we actually see that these agents truly increase overall survival. The argument that we put forward was one where we’re not saying for a minute we should stop research in the targeted therapy arena, into the development of therapies targeting oncogenic pathways, but we also think that there should be a balance, and that balance should be struck around trying to develop new approaches that begin to tackle some of the fundamental problems we see in tumours – namely their underlying diversity that spawns resistance to treatment. And there are many ways we’re thinking this could be done, or this is already being done through the use of optimal immunotherapy approaches or a better understanding of what’s driving tumour diversity and ultimately what’s driving resistance to these targeted agents that we’re using.
Kat: So you’re very in favour of these specific molecular targeted agents, Gerard. Where are you coming from with this?
Gerard: I think we all have to understand that we live in the real world, and ideas go in and out of vogue. And so what I’m anxious about is that targeted therapy is a very young technology, we’re not targeting many things at the moment. We know there are engines that will make much better targets than many of the things we’re able to target at the moment in terms of the drugs that we can make. And I’m anxious that we don’t throw the baby out with the bathwater. If people get the idea that the latest thing is immunotherapy, then everyone’s going to jump on that bandwagon. I think Charlie’s hit the nail on the head – we need a balanced approach. We need to understand that some technologies are embryonic still, and have a long way to go, and I would agree with him that we’re not curing many patients with targeted therapies. On the other hand we do understand much more about the molecular architecture of cancers and what keeps them going, and I think it’s only sensible to think about ways of designing drugs that hit those particular nodes that keep the cancers going. But I would absolutely agree – the debate was not intended to be partisan, it was intended to bring out the issues and to get the audience involved, and I think it was very successful. And Don Ogilvie, who spoke with me in favour of targeted therapies, I know he agrees with me on all of those points.
Kat: One of the interesting things was that Don went through some of the success stories of targeted therapy. We see great success with Glivec for treating certain types of leukaemia. Many people feel the future is in combinations of these very targeted agents. Charlie, you’re concerned about putting all our hope in combinations?
Charlie: I’m much more sceptical about that approach. The rationale for combination approaches is that tumours don’t have one driver, they have many drivers, and we have to target these multiple drivers at the same time, to maximise tumour response. The difficulty is that no individual tumour is going to be the same as any other tumour, so each patient would require their own specific, personalised drug cocktail, if you like, to maximise tumour kill against all the potential subcloncal drivers that are present and operating in that tumour – that is, drivers of tumour biology that are present in some cells but not others, or some sites of disease and not others. I think practically that’s a very, very difficult problem. It’s going to require drug companies working together, it’s going to require drug development programmes across a myriad of different potential driver events, it’s going to require a bias away from what is the current practice, which is developing “me too” drugs where you have six or seven companies developing programmes against one drug target, which we see time and time again, which waste resources. I just practically can’t see that type of therapy developing very far in my lifetime.
The other aspect of this is that a lot of the theories about combination treatment in the clinical setting derive from our experience treating bacterial infections, for example, where we’re used to treating with two or three antibiotics or two or three anti-retroviral agents at a time to treat HIV, for example. And the rationale behind that is that retroviruses, bacteria and humans diverged in evolution billions of years ago, and therefore we can successfully target proteins that are operating in a bacteria that don’t have homologues in human cells. The therapeutic window, on the other hand, in cancer biology is much, much narrower – we’re talking about targeting subtle alterations in gene dosage or subtle alterations in gene function that have on-target effects on the same proteins that are operating in normal human cells. And because of that, the challenge of combining these targeted therapies is much, much greater than it is in treating a complex bacterial infection or a retrovirus.
Kat: And Gerard, your work is trying to target some of the really key ‘gatekeepers’ in all this cloud of targets. Do you think that really going for the most important things is going to be the way forward?
Gerard: I absolutely agree with Charlie – we both are convinced of the value of looking at cancers as evolving systems and evolutionary diseases of somatic cells. But I think he obviously espouses this notion that there are many drivers, and I think there are, and if you knock out one driver then another one may evolve and activate, and then you have to chase that disease down.
Kat: Like whack-a-mole?
Gerarad: Yes, but every time you whack that driver you hit that molecule in normal cells, and you also have off-target effects and your side effect profile spreads out exponentially. But I think there’s a different issue. Hitting the drivers is not what I’m advocating – I’m advocating hitting the ‘engines’. Now there are conserved engines I think cancers cannot do without. There are lots and lots of drivers, for example, of the Ras signalling pathway, lots of receptor tyrosine kinases, and any one of them can do the same job to activate Ras. But there’s only one Ras node there. Ras is the engine, Myc is the engine, E2F is the engine. I think we need to hit the engines and not worry too much about the drivers.
Kat: These are very hard proteins to target with drugs – where are we going to get some new drugs in these areas?
Gerard: Because we need people that are courageous – I think courage is the most underestimated virtue in science – and I think this is exactly the sort of thing we can do in the UK where cancer funding is from independent charities who don’t have to follow trends. We can make brave decisions here, and I think we need to try and make drugs against these engines. Now I don’t know what the side effect profiles are going to be, I don’t know how useful they’re going to be, we don’t know. It is a challenge, but I think it’s a challenge worth fighting for.
Kat: So to sum up, Charlie, what’s your current key challenge going forward?
Charlie: I think one thing we haven’t discussed here is that Gerard and I agree on this issue in general. So I think the problem with a debate is that it’s quite polarised, but in reality I completely agree with what Gerard’s just said. I think another thing Gerard mentioned that we haven’t discussed is this issue of tumours being forced down routes that they must go down – it’s almost as if we’re seeing tumours as being pre-programmed to go down different routes, and if we can understand the biology of that up front it may tell us something more about the routes that tumour will have to evolve through subsequently. I think understanding those routes that tumours must progress through in the future will help us develop better targeted approaches to stop it from happening.
Gerard: I agree with Charlie.
Kat: I loved in your talk that you gave [Charlie], when you talked about it being like a chess grand master, always trying to stay one step ahead.
Charlie: Essentially this is like the most phenomenal game of chess mankind’s ever played against a grandmaster that currently doesn’t exist. And we’re having to predict a move ten moves ahead. So understanding what that move might be could help us make a defensive move up front that stops the grand master from being able to make that attacking move that leads us to fail.
Kat: And Gerard, the debate that we had was absolutely fantastic and lots of people had lots to say. How would you sum it up?
Gerard: I would sum it up as the fact that we are, as always, on the edge of the unknown. There are strong opinions and passions, which I think is great – that’s what drives creativity in science – but there is also healthy objectivity and the ability of people to not be partisan and to be interested in each others’ work. Cancer research is a very broad church, and I think that’s one of the most wonderful components of it.
Kat: That was Professor Charlie Swanton and Professor Gerard Evan. That’s all for this special edition, we’ll see you again at the beginning of December for our regular podcast looking at all the latest cancer news. And if you’re listening to this on Soundcloud, please leave us a comment with your feedback. Thanks very much and bye for now.