Deprivation, Wikipedia, pancreatic cancer and immunotherapy
Kat: This is the Cancer Research UK podcast for June 2014. This month - how deprivation is linked to 19,000 cancer deaths a year, why Wikipedia falls short and how we’re improving it, and the latest on immunotherapy and pancreatic cancer. Plus our heroes and zeros.
Hello and welcome, I’m Dr Kat Arney. In the news this month, we heard the shocking statistic that the poorer you are, the more likely you are to get and die from cancer, with more than 19,000 cancer deaths every year linked to lower levels of income. And there are more than 15,000 people diagnosed with cancer every year partly as a result of their economic deprivation.
The figures come from a new report from Cancer Research UK and Public Health England’s National Cancer Intelligence Network, and also reveal that there has been virtually no improvement in narrowing the gap in the number of cases between the most and the least poor people during the last 15 years.
Our reporter Greg Jones spoke to Matt Wickenden, our Senior Statistical Information Officer, to find out more.
Matt: There’s two main things that this report is showing us that we didn’t know. One is the scale of the number of cases and deaths linked to deprivation, and also it flags an unacceptable lack of progress in tackling that. We’ve even seen for five cancer types an actual widening of that gap which really is a cause for concern.
Greg: So what cancers are we seeing perhaps a real issue? Which cancers do we see that we need to do the most work in?
Matt: One of the biggest factors that we’ve seen influencing the higher rates in the lower socioeconomic groups is those linked to tobacco. So lung cancer alone is responsible for 11,000 excess cases in the lower economic groups. And I think that just shows how important it is that measures like standardised packaging, which will make the packs less attractive to the next generation of smokers. And also stop smoking services that will help current smokers quit, really are key to making a difference in this area, as well as just tackling those cancers generally. I think if there was one big take-home message from this it’s that smoking really does kill and we need to tackle it.
Greg: So tobacco is obviously one of the big factors, but what other reasons are there that the more deprived groups seem to be having a higher number diagnosed with and also dying from cancer?
Matt: So as well as seeing higher smoking rates in the lower economic groups, we’re also seeing that there may be some low awareness of cancer symptoms and less access to GPS. So the issue of early diagnosis certainly is an important one, so we need to keep raising awareness of symptoms. We saw with a health campaign last year called “Be Clear on Cancer” we were able to get 700 extra people diagnosed through a campaign that highlighted one of the main symptoms of lung cancer, which is a persistent cough – some people may have seen that on the radio and TV – and that made a real difference. And we saw that simply getting those messages out there we could get people to their GPs earlier and that, we think, will certainly have saved some lives.
As well as those kind of things people may be familiar with, we also need people to have more access to their GPs, so we want to see people from all groups to be equally able to both access their GPs and equally likely to take up opportunities such as screening – bowel cancer screening, breast screening and cervical screening – which have a very good track record of saving lives. Through taking up those opportunities, people can give themselves the best chance of beating the diseases.
Greg: What would be the key message to both the public listening and also to policymakers and people who are looking at awareness campaigns? What are the key messages we need to be communicating to them to try and close that gap between those who are more and less deprived?
Matt: There’s no way that tobacco couldn’t come out as the biggest issue here, so we really need effective measures to tackle it. So that’s standardised packs, and also ensuring that the good work of the NHS Stop Smoking services can continue. We’ve seen thousands of people quit through their work and that investment needs to keep coming. But we also need people to be aware of any unusual changes in their body and what’s normal for you, and take action if you see [anything], because that gives you the best chance of beating the disease if you do have it. And there’s a good chance if you do have anything [unusual], it won’t be anything, but you can give yourself that reassurance.
And finally, just ensuring that the services, the NHS, are successfully targeted at the people that need them most. And we’re seeing with this report that clearly there is a big need in the lower economic groups. It just shows that it isn’t right that people’s background should be determining their risk of getting and dying of cancer, so we really need to find some answers to tackle this to be able to save more lives.
Kat: Matt Wickenden there.
Our researchers have made progress against pancreatic cancer this month, with two papers revealing new insights into the disease and pointing towards potential new approaches for treatment.
The first, from Dr Laura Machesky and her team at our Beatson Research Institute in Glasgow, showed how high levels of a protein molecule called fascin helps pancreatic cancer cells spread into the abdomen. But when the protein is missing, the cells can’t go on the move. Developing drugs to block fascin could potentially prove to be a way to stop pancreatic cancer spreading round the body, as well as certain other cancers that also have high levels of the molecule.
The second research story, from Professor Duncan Jodrell and his team at our Cambridge Institute, highlights how pancreatic tumours can break down the drug gemcitabine, which is commonly used to treat them. The scientists discovered that gemcitabine gets broken down by parts of an important biological pathway in cells – called the Kennedy Pathway – which cells use to make special fats.
Their findings suggest that adding a type of fat called linoleic acid in combination with gemcitabine increases the amount of the drug in tumour cells, which might make it more effective, although more work still needs to be done to figure this out.
We’re particularly focusing on pancreatic cancer as part of our new research strategy, which we talked about in last month’s podcast, aiming to boost the current poor outlook for patients, with only around four in every 100 surviving the disease for five years or more. Although it’s still early days, these new results are another step in the right direction towards more effective treatments in the future.
According to a new study, Wikipedia, the online encyclopaedia that can be edited by anyone, contains errors in nine out of 10 of its health entries, and should be viewed with caution by people looking for accurate information. It’s the work of researchers in the US, who compared entries about conditions such as heart disease, lung cancer, depression and diabetes with peer-reviewed medical research.
They said most articles in Wikipedia contained "many errors", with around nine in ten pages they looked at containing statements that contradict the latest medical research. But while the internet should never be a substitute for medical advice from a real doctor, there’s a bit more to this story than saying it’s completely unhelpful. Our reporter Greg Jones spoke to John Byrne, our very own Wikipedian in Residence here at Cancer Research UK, to find out how reliable Wikipedia – as well as this study – actually is, and how we’re working to improve things.
John: We have a very active medical Wiki project, it’s called, which is essentially the group of regular editors on the English language Wikipedia who are interested in medical content and edit it. Actually the great majority of the editing is done by about 30 people, and most of those are medical professionals of various kinds, or have got degrees in related subjects.
Greg: Is it surprising to see that they’re saying something like nine in 10 of these pages do still contain errors? Is that because of the wealth or the volume of information?
John: That particular study I don’t think – particularly as it was reported by the press – wasn’t accurate. The study itself had severe problems which we don’t have time to go into but I start addressing that on the blog. So I don’t think the level of inaccuracy is anything like that high. There are questions of completeness and balance and so forth, and part of my role is to bring all the different kinds of expertise within Cancer research UK to bear upon the cancer articles on Wikipedia, working with the existing medical editors, who are very keen on this, to improve them.
Greg: Your role here – you’re our Wikipedian for us – what does that role actually involve?
John: The first aspect is working bringing together Cancer Research UK’s expertise with the existing Wikipedia editors, and hopefully more Wikipedia editors that I can recruit, to improve cancer-related articles. So that’s one big focus. Another aspect is to conduct some research into the experience of users of Wikipedia, and how Wikipedia fits into a search for information on cancer using online sources.
Greg: So do you think that more organisations, health charities and others, should be looking at doing a similar sort of programme to help improve information that people can find online?
John: There’s quite a lot going on, particularly in the States. The Cochrane Collaboration actually has a Wikipedian in Residence. There’s quite a lot happening in American medical colleges especially – some of those have an optional course element which involves writing or improving articles on Wikipedia. There’s much less of that in the UK. This project involving me is funded by the Wellcome Trust and I think people will be looking to see what the outcomes are, and hopefully other projects will follow.
Kat: That was John Byrne talking to Greg Jones – you can read more about our involvement with Wikipedia in John's post for our Science Blog – just follow the link in the SoundCloud player. And as John mentioned, although we're working to make sure that the information about cancer on Wikipedia is as accurate as possible, and it's understandable that people will want to research medical conditions on the internet, it's not a replacement for talking to your GP or other medical professionals.
Every year at the beginning of June, cancer researchers from around the world head to the States for the ASCO meeting – probably the largest cancer conference in the world – to hear about the latest advances. This time the headlines coming from the meeting were all about immunotherapy – treatments that harness the power of a patient's own immune system to seek and destroy cancer cells – which are starting to show very exciting results in early stage clinical trials.
In particular, there was a lot of buzz about drugs targeting T cells – our body's 'army' - including drugs blocking important immune 'brakes’, such as the molecules PD-1, PD-L1 and CTLA4. To find out more about the science behind the headlines, our reporter Alan Worsley caught up with Professor Sergio Quezada at University College London.
Sergio: So the treatments that are generating all the fuss and buzz are based on...they are simply antibodies. And what they do is they make the immune system extremely powerful at either recognising or running after cancer cells in a way. The two main antibodies that are appearing and that people are talking about - one is against a target called, molecule called, CTLA4 and another is to a molecule called PD-1 and basically what those molecules do is that they are truly like brakes of the immune system.
So whenever they are on immune cells they are breaking the function of the immune cells. They are stopping those cells to work. So these antibodies what they do is basically they release the brake on the immune response and then the T cells just go crazy after the tumours. And are able to go inside the tumour to destroy the tumour – that is basically what these therapies do.
Alan: So the immune system normally should be attacking these tumours – but these tumours are finding a way to – as you say – activate the brakes. So these treatments are sort of preventing them from the stop sign coming up.
Sergio: In many cases it is releasing the brakes so the T cells will go after the tumour. And then in other cases it depends on the type of drug. For example, when cells get into the tumour the tumour is able to put up this shield – people call it the molecular shield. And basically what one of these antibodies does is prevents the shield from coming up or it blocks the function of that shield. So your T cells can now really see the tumours out of the gate. Here you are - here is the payload and they deliver the goodies that they have to deliver in order to kill the tumour.
Alan: So the T cells in this case are sort of the generals of the immune system aren’t they? They’re the ones that organise the fight. There are whole different branches, but they are the main ones to fight the cancer cells aren’t they.
Sergio: So in the case of cancer, T cells are some of the ones that can do a really big push against cancer cells and really destroy cancer cells. And at least this therapy, what they do is they unleash the function of these T cells, but when those T cells go and kill a tumour - then the rest of the army also gets activated.
So that’s the beauty actually of immunotherapy is that unlike other therapies, like conventional therapies like chemo and radio, your therapy ends when you are given the drug – your therapy finishes, right? In the case of immunotherapy you are given the drug that releases the brakes on your immune system and then you withdraw and the immune system keeps on going and keeps on going and actually continues to evolve and to spread. So you start with T cells very important and then you get all of these other cells coming in and really getting activated cause now you flagged that site. You put a big flag that said here there was trouble and we need to deal with it. SO that’s basically what immunotherapy does.
Alan: So why do you think these sort of suite of different therapies – they’re all slightly different – but why are they coming out now? Where did this start? When did this become an attractive mechanism to try and stop cancer?
Sergio: So it’s all based on research and the time that it takes to do the research, to the time that it takes to make discoveries and actually reanalyse those discoveries. And say: “were we right? Were we correct or not correct on the conclusions that we took based on the initial data?”
So the field of immunotherapy is actually quite old and people have been working on ways to mobilise your immune system to cancer for actually many, many, decades.
But in the case of these molecules that we are talking about now, for example CTLA-4 was discovered in the mid 80s, right, so that molecule somebody said: “oh there is a new molecule, CTLA-4” and actually people did research up to the mid 90s trying to understand how CTLA-4 worked and they thought that actually CTLA4 was not a brake, it was an accelerator of the T cells. They were completely confused and that’s because the way the experiments were done. And then people continued to do even more research and asked: “Are we right about that? Are we correct or incorrect on our conclusion?”
So then in the mid 90s a number of experiments came up, almost at the same time. That’s how science works, like the good science always comes out at the same time in different labs. And they demonstrated that actually it WAS a brake - that CTLA4 was a molecule that prevented T cell function.
And then a year or two years later Jim Allison published his paper saying that “Oh I made an antibody that can actually block this immunological brake.” And he tested that in animal models of cancer and the tumours melted away.
And at that moment, in 1996 I think it was that paper, people said, “we have now a molecule that can release the brakes on the immune cells.” And I guess at that moment pharma said this is what we should be looking at. So we are talking about many, many, years ago that people found the molecule - were lost on how it works - then they discovered really how it works – then they started trying to design ways to use that knowledge in order to promote a new, or generate a new future clinical trials. And obviously then you go into the difficulties of generating a drug that you can give into humans, the initial early phase clinical trials etc etc.
So it takes a long time but it’s because we’re building on knowledge and actually trial and error which is what happens in science. I don’t know how many scientists participated on the whole discovery of CTLA-4, to the understanding and then to the design of the antibody.
For example, CTLA 4 was discovered in France, in a laboratory in France, that’s where it was cloned. And then most of the other work was done within the States and Europe, in terms of understanding how it works and then in California Jim generated these antibodies that could block the function.
We could say “well we spent a lot of time without any drugs that are working against cancer.”
Yeah it’s because we are building on knowledge, we are doing science trying to understand how can we use these drugs or these concepts in order to cure cancer.
And the pipeline continues to accumulate - the same way CTLA4 was discovered in the mid 80s, a couple years later PD-1 was discovered, which is the other beautiful poster child of immunotherapy now. And then it took a couple of years to understand how it worked and a couple of years to say, “Yes an antibody that blocks this pathway will also release the brakes etc etc etc.”
So it takes time, but it’s not because we are just not doing anything and this molecules magically appear. It’s because scientists are really working trying to get the best answers and the best knowledge out of this.
Alan: How promising do you think these drugs are?
Sergio: Personally, I think they are a complete game changer. So I think that the scientific community, besides the cancer immunologists, now the rest of the scientific community sees this as an approach that is really extending, in some cases, extending the life of patients. In many cases producing complete responses, or at least incredible tumour regression. And the responses are durable in most of the cases are durable. And that has been always a problem – how to get durable responses.
So I see it as a very promising way to treat cancer. There is now - because more people believe in it based on the data that is coming out - There more scientists and more clinicians we need to collaborate in order to generate the next trials. So now there is a large number of different trials in Europe and in the States trying not to say, “ok is this pathway important”, or “is this molecule important” “this other molecule...” – can we combine them now.
So there are trials to combine the different drugs and basically really step on the accelerator and release the brakes of the immune system. And there are even a number of trials combining conventional therapies with immunotherapies - because that also makes sense. You can kill the tumour by giving chemo or radio and then you can unleash the force of the immune system on top of that tumour. That is kind of banging, like a little bit dead.. you make him struggle a little bit with chemo or radio or the new targeted agents and then you hammer them with the immune system. You generate this immunological memory that will allow the immune system to continue attacking that tumour.
So I think it makes sense. It always made sense, at least for us working in cancer immunology. The preclinical studies show that this could work. But we needed to see the clinical data, the phase three trials or the large phase I/II trials. And the data is coming up. And it’s showing that it continues to be promising. This time it’s for real I think.
Kat: That was Professor Sergio Quezada from UCL talking to Alan Worsley. And you can find out more about this new generation of immunotherapies on our Science Blog.
Now it’s time for our heroes and zeros, and we’re starting with our zero – uncritical media reports of the world’s first ‘drinkable sunscreen’, created from so-called "harmonised water". Just a couple of drops every few hours is supposed to protect your skin from the damaging UV rays that cause ageing and - in the worst case - skin cancer. It sounds too good to be true - and, at least in terms of any kind of scientific plausibility, it is. To find out more about how it's meant to work, and the best ways to genuinely protect yourself, I spoke to our Senior Science Communications Manager, Nell Barrie.
Nell: So on the surface of it, this does look like “wow, what an amazing innovation!” but looking into it further, it does appear that in fact it is just water. Literally, just water. So all this talk about “imprinting things on the water”, essentially it's just water in a bottle. So there's really no way that science knows of that this can possibly help to protect your skin against the effects of the sun.
Kat: I think the idea is that they've imprinted some kind of 'wave' on the water and that somehow magically makes it onto your skin and stops the UV. People have been trying to sell water in a bottle for curing all sorts of things for many hundreds of years – is this just a slightly more sophisticated version?
Nell: It does seem to be based on that concept. In the same way that homoeopathy is said to rely on the “memory of the water”, again there's no scientific theory that could explain how that would be possible. So you've literally got some water in a bottle. Drinking a couple of drops of this water is not going to protect your skin against the sun. There's just no way we know of that that could possible happen.
Kat: And is there any actual scientific evidence that they've provided that this is protective?
Nell: At the moment no. We've heard things like “It's based on a new type of science”, but that's not any kind of evidence that will stand up to scrutiny by people who are experts in this area. So, no evidence at the moment.
Kat: And, I'm assuming, no clinical trials?
Nell: Definitely no clinical trials – as yet!
Kat: I've also seen some things talking about sunscreens that you could eat, about things like eating foods very rich in lycopene like tomatoes, or things like beta-carotene found in carrots and all kinds of fruit and vegetables. Would these be a viable alternative to slapping on the hat and the sunscreen?
Nell: It's such an attractive idea, isn't it? I've always thought wouldn't it be great if you could just take a pill instead of having to put the sunscreen on before you go out. But at the moment, even if you're doing things like taking in things like antioxidants that can help to protect your cells from damage in some circumstances in specific ways, it's not as easy as just saying “eat more of them, they'll go into your skin and you'll be protected”. We just don't know enough about exactly how all these processes work to be able to say things like that at the moment.
Kat: So what is the best way to protect you skin this summer? Both you and I are very pale ladies – how should we be protecting our skins from the damaging effect of UV rays?
Nell: Well, really, the key thing is to try and not expose your skin too much to the sun – that's the crucial thing you've got to bear in mind, So from that perspective, sunscreen is useful but you shouldn't be relying on sunscreen to protect yourself. You should be making sure that you're staying in the shade when it's really strong, covering up with clothing, definitely wearing a hat – all those things are really important and more effective than using sunscreen. Sunscreen is if you can't protect yourself and cover up in other ways – that's what sunscreen is for.
Kat: And what sort of sunscreen should we be looking for? There's an array of bottles in the pharmacist's – is it worth going for the really expensive ones? The cheap ones? What should I look for.
Nell: What people should be looking for is at least SPF15, and look for a high star rating – that's the UVA protection you get. You want to get as high a star rating as you can. You don't have to pay a lot of money for that. There's own brand makes that have really high star ratings and are really effective, so just keep an eye out and make sure it's got that high quality star rating.
Kat: That was Nell Barrie. And finally, our hero this month could be nobody else but Stephen Sutton, the inspirational 19-year-old who raised millions of pounds for the Teenage Cancer Trust charity before dying of bowel cancer in May. His positivity and courageous spirit is an inspiration to all of us who are working towards beating cancer for good.
That’s all for this month, 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 firstname.lastname@example.org, 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.