Prostate and childhood cancer progress

Cancer Research UK
We discuss how the immune system may act as an early warning alarm, sleeping cells, progress in prostate cancer and children’s cancer trials.



Kat Arney: This is the Cancer Research UK podcast for December 2013. This month we’re discussing how the immune system may act as an early warning alarm, sleeping cells, progress in prostate cancer children’s cancer trials. And we’ve got this month’s heroes and zeros.

Hello and welcome. I’m Kat Arney, and with me to discuss the latest news is Nell Barrie, Senior Science Communications Manager at Cancer Research UK. What’s the first story you’ve got for us?

Nell: So this is a really interesting story looking at the immune system and cancer, which is always a fascinating area, and it’s done by some of our scientists in Leeds and at The Institute of Cancer Research in London, published in Nature Medicine. What they’ve found is that when cancer’s go into remission, from the outside it seems like there’s no more cancer present, you can’t detect it, but in fact there are small groups of cancer cells that can hide away inside the body, and they can lie dormant until they become able to grow again and cause the cancer to relapse.

Kat: So this is cancers coming back after they seem to have been treated successfully?

Nell: Exactly. And what is interesting is that it seems that we can actually predict when that might happen, because we can see the immune system start to react to these cancer cells coming back.

Kat: Because that would be really useful – at the moment you just have to wait until the cancer can be detected on a scan or is big enough for someone to feel a new lump. How did they find this out?

Nell: What they’re looking at is the way that the cancer cells change over time, and the idea with this research is that they’re sitting there in the body, they’re gradually evolving to be able to break fee free from the immune system that’s kept them under control, and that’s the change that you’re seeing when the immune system starts to react again.

Kat: How have they done that? Have they done this looking in patients or is it something they’ve just done in the lab?

Nell: So far this is just in mice, and obviously mice can be a very useful model for this type of work but we don’t know whether this is replicated in humans yet, and we’ll have to do a lot more research to find out if this is something that could help to detect early cancer recurrence in patients. But it’s looking really interesting, and it could be potentially a really useful way to spot cancers a little bit earlier as they start to come back.

Kat: And one of the things I thought was interesting from this research is that there could maybe be a change in the way that we treat cancers that might be coming back. They talk about perhaps you could ‘wake them up’ using the immune system, and then treat them before they’ve become really dangerous. And that’s an approach that’s already being used for some types of cancer.

Nell: Absolutely. And on the face of it, it sounds a little bit scary, saying we’ll wake the cancer up, but the thinking behind that is that if you do that at this early stage, the cancer’s actually more vulnerable to treatments that you could use to get rid of those new cells. So the cancer hasn’t quite got up to its full power yet, and it could be a much better time to treat it. And we do already do that, for example, with thyroid cancer. Patients are given a hormone that stimulates the thyroid, and that can actually reveal any hidden cancer cells so they can be given more treatment before the cancer comes back more severely.

Kat: But the key thing there is there’s really effective radiotherapy treatment for thyroid cancer, so if you’re going to wake a cancer back up, you really need to know you can knock it back down again, I guess.

Nell: Yeah, absolutely. And this is why we need more research – we need to know that if we do use this ‘waking up’ method, then we’ve got treatments that will really knock the cancer on its head once you’ve done that.  But it’s a very interesting way to look at how the immune system and cancer work together, how they interact, because we know there’s a lot of complicated stuff going on there. Learning more about that will be really useful for the future.

Kat: And another story about waking cells back up was some research I saw from our scientists at the Beatson Institute in Glasgow – they’ve published this in Nature Cell Biology. What they’ve been doing is looking at ‘sleeping’ cells, these are called senescent cells, and these are cells that as they age they basically shut down and go to sleep. They stop multiplying, and this is a really important way of bypassing cancer, because obviously if your cells can’t multiply any more they can’t become a tumour. And they’ve been studying in really great detail some of the genetic changes in these cells, but not at the level of genes being faulty, but at the level of these molecular ‘tags’ that switch genes on and off. What did you get from this story, Nell?

Nell: Well I think this is really interesting because we think of cancer as a disease that people get when they’re older, but as one of the researchers points out, we don’t actually know very much about why that is. We’ve got a lot of ideas about cells developing mutations over time, but, as you say, this is a slightly different level of genetic change they’re looking at. It’s cells that have got old, they should be switching themselves off but in some cases they can actually bypass that process. And because they’ve gone through this ageing process, they have different tags within the cell that change the way the genes are functioning. And that could, in fact, mean these older cells could go on to create cancer later on.

Kat: It was really fascinating that the changes that have happened in these cells almost leave them ‘poised’ to become cancer cells. Normally they would stay asleep, but if for some reason that gets bypassed and they switch back on – I think one of the words to describe it was like a timebomb, that these cells were almost ready to become cancer cells. Mostly they don’t but sometimes they can. This was very early research that was done but they did find that ageing cells are very similar to cancer cells in terms of these switches, these molecular tags. So it does tell us a lot about how do our cells age? Why is cancer a greater risk for older people with older cells.

Nell: Absolutely, and the researchers were obviously really fascinated by this signature they could see in the older cells which really mirrored what you see in cancer cells, so that was really fascinating to see it was so close and so similar. So I think it’s really about understanding exactly what is going wrong in these cells, what’s gone wrong in cancer cells, are there similarities that we could use to find new ways to treat it, and maybe find ways to prevent it from happening in the first place.

Kat: And understanding why the risk of cancer is so linked to ageing in most people – I think that’s still a big mystery that we don’t know a lot about. And finally we’ve got a bit of an update on the Francis Crick Institute, which, last time you saw it, was an enormous hole in the ground near King’s Cross. What’s the Crick, Nell?

Nell: So the Crick is a really brilliant new research institute that we are helping to build near King’s Cross. The idea is that there will be researchers there covering many different types of medical research. Not just cancer, they’re looking at infectious diseases, cardiovascular disease. The vision is that you’ll have all these amazing minds in the building, working in quite similar areas although on different diseases, and hopefully they’ll come to some really fruitful collaborations by all being in one place.

Kat: I think one of the great things about the Crick is that it’s very cross-disciplinary. So it’s not all about just getting biologists in a building, it’s about biologists and chemists and mathematicians and physicists. One of the people who’s actually on the board of the Create the Change campaign, which is raising money to build the new Crick Institute is a chap called Mike Lynch. He’s a technology pioneer, and our reporter Simon Shears met him at a recent breakfast meeting to find out more about some of the plans for the new institute.

Mike: Well what we’re doing today is we’re having a little breakfast talk about innovation. One of the themes for today is going to be about how important crossover is to innovation. So for example in cancer research at the moment, people think about scientific test tubes and ‘wet things’ but actually one of the most important areas that’s coming into that area is using advance mathematics to understand all the data that’s being generated.

And so that’s what we’re going to talk about today – a little bit of crossover and explain some of the work. And for example the Crick Institute, one of the wonderful things about is that in the same building we’re going to have groups of people from these different backgrounds allowing you to unite in actually learning how to deal with cancer.

Simon: Who is here today? Who makes up the audience?

Mike: What we’ve got today is a large cross-section of people who have some reason to want to learn about the work at the Crick Institute, and hopefully support that work. And they range from people who work in the City, to people from the media world. Now what we’ve got here I’m afraid is a rather rainy, grey morning in London but hopefully we can light it up with really pointing a way to the future.

Simon:  And finally, being involved in ‘Create the Change’ and the Francis Crick Institute, what does that mean for you?

Mike: Well, I think we’re at a very important time, so, the difficulty is cancer is an incredibly complex disease. A cancer cell is fighting for life just in the way our own cells are. And what’s happened is that over the years we’ve really learned the complexity of that and we’ve had some good effect moving forward and finding cures.

What’s happening now is especially with the new science of genetics and the ability to sequence information inside a cancer, we’re opening up a whole new approach to doing cancer research and getting results.

Kat: That was Mike Lynch talking to Simon Shears. So everything seems to be going to plan as far as we know?

Nell: Absolutely. It’s amazing the progress that’s been made. Like you said, when I saw it initially it was a big impressive hole in the ground, but still there was no building there. And I actually went past on the bus a few weeks ago and it’s starting to look like the real building. It’s really exciting and everybody’s looking forward to when that opens and we can see inside, get all the researchers in there and get the research actually happening.

Kat: Fingers crossed that will be happening from 2015. Thanks very much Nell, that’s Nell Barrie.

Nell: Thanks.

Kat: There’s been a lot in the news over the past month about prostate cancer, and there have been several key breakthroughs in recent years including the drug abiraterone, also known as Zytiga, which our scientists helped to develop.

To find out where we currently stand in the fight against prostate cancer, how things have improved over recent years and the key challenges for the future, our reporter Alan Worsley spoke to Professor Nick James, our prostate cancer expert at the University of Birmingham.

Nick: It’s actually a very exciting time. For men with advanced disease we’re seeing prognosis improve hugely because there’s been a series of very important new drugs licensed over the last ten years, and we’re seeing big improvements in survival in patients with incurable disease in my clinics.  

At the other end of the spectrum we’ve got an increasing understanding that not everyone diagnosed with prostate cancer needs necessarily to be treated – they do need to be monitored but they don’t need to be treated. And I think we’re going to see an increasing role of imaging – multi-parametric MRI in particular – to try and stratify those who need treatment with early disease from those who don’t.

And there’s all sorts of exciting data coming out of the genetics of prostate cancer that I think will also help to stratify people into those that are likely to get prostate cancer and therefore may benefit from screening from those who are really very unlikely to get it, and who you might not want to screen at all. I don’t think at the moment we should be screening with the state of play with the PSA test.

At the opposite end of the spectrum, 10,000 men a year roughly die of prostate cancer in the UK and ten years ago we had pretty much no treatments for them, once standard hormone therapy – which is the mainstay of first-line treatment – failed. And there’s been an explosion of understanding of what’s happening when patients relapse on hormone therapy, and off the back of that, new treatments that genuinely improve outcomes both survival and palliative benefits rolled into one.

Alan: So when you say we’ve got some new treatments available, is that all quite recent?

Nick:  So the first major change was the licensing of docetaxel in 2004, so that’s obviously a chemotherapy drug and that was a really important paradigm shift, as it was the first time that any treatment had been shown to prolong survival in relapsed prostate cancer, and also to produce palliative benefits, which is always a bit of an oxymoron in patients having chemotherapy. But undoubtedly patients with things like pain got better on the treatment, and so you had a palliative benefit to offset against the side effects of the treatment, which are actually quite modest.

There’s also been a lot of interest over why do patients respond so well to hormone therapy? Well over 90 per cent of patients respond to androgen deprivation, but then they relapse, somewhere between one and three years later depending on how much disease they had in the first place. And it used to be thought that these patients were ‘hormone independent’ or androgen independent, but actually it turns out that to a large extent these tumours remain androgen driven, and they get around this in essentially two ways.

One is that they start to make their own androgen inside the cancer cells, and the second is that they mutate the androgen receptor so it’s stimulated either by lower levels of androgen or other ligands, such as other steroids. And once that was worked out you can start to design drugs that target it. So you can produce androgen synthesis inhibitors, and abiraterone was the first such drug to be licensed in 2011, or you can produce better ways of targeting the androgen receptor.

There were androgen receptor targeting drugs around already, but not very good ones, frankly! So better drugs that target the mutated receptor in the androgen-resistant cells have turned out to be very effective – so enzalutamide is the first such example of that. There will doubtless be other examples of both classes of drug. So those were both important new advances.

The interesting question, obviously from my point of view as an academic, is that once you know something works, can you use it in a better way?  So taking the example of both docetaxel and abiraterone, we’ve got a study running called STAMPEDE where we’re using both of these drugs instead of at relapse, as first line treatment at diagnosis.

It’s a trial we’ve set up in a slightly unusual way. Instead of having a binary question – a control versus the new treatment – there are a number of new treatments we might want to evaluate all at the same time. So we had a multiple arm trial, and we also built into the trial multiple stages. At intervals we look at the data and decide whether there’s any impact at all on time to failure. If time to failure is improved, the drug stays in the trials. If it’s not improved or not improved enough the drug goes out of the trial.

So STAMPEDE started with three drugs – docetaxel, zoledronic acid, and celecoxib.  Celecoxib failed one of these interim rounds of the ‘high jump’ contest, if you like but the other two drugs, docetaxel and zoledronic acid, passed the interim stages and stayed in the trial all the way through to complete recruitment, which they did earlier on this year. So we’ve got around two thousand patients in each of those randomisations, and we’re currently in follow-up and we’ll have an answer as to whether up-front use of those drugs improves survival in about 18 months time.

Subsequently abiraterone was developed and was clearly going to get a licence, so we thought ‘well this is a drug we also want to put into the trial’. So, again, the trial wasn’t necessarily designed this way in the first place, but we realised that the design would allow us to add in new arms, starting after the original ones. So we added in abiraterone as an extra arm, and we’ve got proposals to add in further new arms in the future of other drugs, for example radium 223 we would like to add in the future.

Alan: Where do you see us in ten years? What do you think is going to be the most effective advance or change to how we monitor prostate cancer?

Nick: I think at the early disease end of the spectrum we’ll have better tools for molecularly profiling people as to whether they are at risk of significant prostate cancer or not, and we will then I think be able to target screening to the high risk groups only. I think that will transform the debate about whether to screen or not.

I think the other thing that will get solidly established is much better imaging. I’ve already mentioned multi-parametric MRI, and choline-PET also looks very promising as a way of identifying small metastases. I think better imaging and better profiling will allow us to better target more aggressive treatments to patients with higher-risk disease who currently we’re not quite sure how to diagnose. And also less treatment or less screening – or no screening, indeed – for patients who are at low risk.

Kat: That was Professor Nick James talking to Alan Worsley. December is traditionally childhood cancer awareness month in the UK, coinciding with the launch of our annual Little Star awards in partnership with TK Maxx, celebrating the courage of children with cancer.

Although three quarters of children with cancer are now cured thanks to advances in research, compared with just a quarter back in the 1960s, around 250 children still die of cancer every year in the UK.

Professor Pam Kearns heads up the Cancer Research UK clinical trials unit in Birmingham, and leads our Children’s Cancer Trials Team, helping to bring new treatments to kids with cancer across the UK.  Alan Worsley met up with her to find out more about the picture has changed for children with cancer over the years, and what still needs to be done to save young lives.

Pam Kearns: In Birmingham we host the children’s cancers trials team, and the aim of this is to develop clinical trials to improve the treatments of children with cancer. We want to try and shift from this idea of eight out of 10 children being cured from cancer – that’s the average. There are some childhood cancers that are very difficult to cure – particularly some types of brain tumours and some types of leukaemia, which are very curable but are associated with lots offside-effects.

We took over the national portfolio of clinical trials in the UK three years ago and our aim is to develop clinical trials that are going to incrementally improve treatment for children with cancer. At the moment, we have clinical trials open for two thirds of children who are diagnosed with cancer anywhere in the country. They will be able to participate in one of these trials. And over the last three years we’ve been developing an increasing portfolio and, by the end of 2014, we will have opened a clinical trial so that eight out of 10 children will have a clinical trial available to them at diagnosis.

The most extraordinary thing about childhood cancer is that families agree to participate in these trials. The majority of children are recruited onto a clinical trial if it’s available to them. This allows us to slowly make incremental progress that is going to increase the quality and effectiveness of treatment in the future.

But this is using drugs that we’ve had around for a long time and what we need are new and innovative ways to treat children with cancer. So the other part of the portfolio is new, innovative trials – small trials – treating very difficult to treat cancers. So we have a portfolio of trials that are now open and developing. Particularly for a disease called neuroblastoma, there’s a very aggressive type of neuroblastoma that is difficult to treat with the drugs we already have, we’ve now got three trials open for this type of cancer.

Alan Worsley: So there’s more and more trials that are opening up to give more research to help answer these questions, both quicker and also more refined. What makes it so difficult to research into children’s cancer? Is it fundamentally different from adult’s cancers?

Pam: Absolutely – so when a child gets cancer it’s not just a small version of the types of cancers that adults get. They have very childhood-specific cancers that are what we call embryonal cancers. These are developing from early tissues where a mistake has happened in that tissue and they develop a very specific type of cancer that isn’t seen in adults.

Now the difficulty is that most drug development has been focused on the types of cancer that you get in adults, and we use those drugs and translate it into children.  What we really need in the future is to understand the biology of childhood cancers – and there’s a huge amount of research going on for that – and to take that knowledge and to develop drugs specifically at the biology of childhood cancers. And once we do that, and can target drugs specifically at childhood cancers, then we’re going to make the progress that is going to close that gap from eight out of 10 children being cured hopefully closer to 100 per cent.

Alan: We’ve had successes based on using adult treatments for children, learning how best to refine those treatments, but what is available today? What trials are going on in the near future that are innovative for children’s cancers?

Pam: So there are a number of trials that we’re running from the trials unit that can answer that question. One is a trial called BEACON, which is a trial for neuroblastomas. So this is a trial for children who’ve failed all conventional treatment – and we’re looking for a new way of treating them – and we’re investigating a particular drug called Avastin (bevacizumab), which is licensed for some types of adult cancers but hasn’t been tested in this type of childhood cancer.

We know from the biology of neuroblastoma that targeting the blood supply using this type of drug, in the laboratory, looks like it has a good effect, but it hasn’t been tested in the clinic. So this trial is asking the question “can you combine Avastin safely with other drugs to treat neuroblastoma and, if you combine it, does it add something to the drugs we’ve already got?”

BEACON is what we call a Randomised Phase II study, so there are four arms to it: some of which are adding this new drug, bevacizumab, to other drugs to see if we can get a better effect but safely. And this trial is already open in the UK, run by Professor Andy Pearson at the Marsden, who collaborates with our unit. We’ve got patients already recruited in the UK but, in order to get quick recruitment so we can answer the question within two years, we’re going to open the trial in 26 sites across Europe.

Alan: So this is a bit of a turning point, in the sense that we’re combining the basic biology and learning about how children’s cancers work and using that to find new ways of tackling these diseases – would that be fair to say?

Pam: That’s absolutely right, and the Holy Grail is to actually develop similar sort of targeted therapies for all types of childhood cancer. At the moment, as I said to you already, Avastin is only licensed for certain types of adult cancers, for example, kidney cancer. But we’d like to take these drugs early in the pipelines, so while they’re being developed for adult cancers we’re already looking at them in childhood cancer and seeing if we can find which ones are effective in childhood cancer.

And, really importantly, can we develop unique drugs specifically for childhood cancer that aren’t necessarily important in adult cancers? That is a really big challenge because it’s a rare disease and we need to really focus on academic development to invest in specific childhood cancers and specific childhood cancer pathways.

Alan: So a great increase in children’s survival in the last 30 or 40 years, and would you say in the last five to 10 years there’s been an increase in knowing exactly what to do? And what would you like to see in the next five to 10 years?

Pam: So you’re right, the last five to 10 years has brought a huge amount of knowledge about childhood cancer biology – that’s absolutely the case. And what we need to do over the next five to 10 years is to translate that into the clinic, get drugs that are targeted specifically for childhood cancers, do clinical trials to check that they’re safe and they’re better than what we’ve already got – so that we have treatments that not only work better but also have less long-term side-effects. So when children grow up, as survivors of childhood cancer, they’re not suffering the side-effects of the drugs they had as children.

Kat: That was Professor Pam Kearns.

And finally, it’s time for our heroes and zeros.  Our heroes this month are all our Little Stars and their families, who’ve all shown incredible courage in the face of cancer. Anyone can nominate a child with cancer to be a Little Star, and every single one will get a trophy and other goodies.  You can find out how to nominate a Little Star on our website – just search for Little Star Awards or follow the link in the podcast player.

And our zero this month comes from a new report looking at how electronic cigarettes, or e-cigarettes, may be marketed to children. Researchers at the University of Stirling sifted through nearly 1,000 pieces of e-cigarette marketing from the past year and found that they used a range of techniques that are likely to appeal to young people, including celebrity and pop star endorsements, social media, mobile phone apps and competitions. One advert was even spotted in an iPad game.

We’re not opposed to e-cigarettes being marketed to adult smokers and we certainly don’t want to see them banned, but we’re concerned that e-cigarettes are being promoted as the latest cool thing to young people. There are also fears that tobacco companies – who have already heavily bought into the e-cig market - will use e-cigarettes to gain access to politicians and public health policy makers, gaining influence and respectability.

That’s all for December’s podcast, we’ll see you again next month for a look at all the latest cancer news.

We’d also like to answer your questions in our podcast, so please email them to, post on our facebook page, or tweet us – that’s @CR_UK. And if you’re listening to this on Soundcloud, please leave us a comment with your feedback. Thanks very much and bye for now.