Liquid biopsies, the Cancer Drugs Fund and bowel cancer

Cancer Research UK
We discuss liquid biopsies for cancer patients, finding out about the Cancer Drugs Fund. Plus, we’re focusing on the progress we’ve made beating bowel cancer.

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We discuss liquid biopsies for cancer patients, finding out about the Cancer Drugs Fund. Plus, we’re focusing on the progress we’ve made beating bowel cancer.

Transcript

Kat: “This is the Cancer Research UK podcast for May 2013. This month we’ll be looking at liquid biopsies for cancer patients, finding out about the Cancer Drugs Fund – and what happens when it runs out. Plus, we’re focusing on the progress we’ve made in beating bowel cancer and the challenges that still lie ahead. And we’ve got this month’s heroes and zeros.

Hello and welcome, I’m Dr Kat Arney, and with me to discuss the latest news is Henry Scowcroft.

Now the first paper I want to talk about is the idea of “liquid biopsies” – I guess blood tests for cancer. What’s this?”

Henry: “So for a long time researchers have been trying to find signals in the blood that tell things like whether a patient has cancer, what sort of cancer they have, how it’s responding to treatment, is it starting to grow again? And this has been a huge focus of research for many years. Most of that research has been trying to look at the proteins secreted by a cancer into the bloodstream – a classic example is the PSA test for prostate cancer. But what’s going on here is actually a much, much more exciting technology. They’re looking at the DNA released by tumour cells into the bloodstream, and this allows them to look not just at whether a tumour is there or not, but what it’s doing, how it’s going to respond, how it is responding, and what it’s made of.”

Kat: “We covered a story very similar to this last month, and this story’s also from researchers at our Cambridge Research Institute, where they looked at changes in a handful of genes in this DNA in the blood – it’s called circulating tumour DNA. How is this new paper a step forward?”

Henry: “So that last paper was very much a proof of concept, and they took a handful of genes that they knew would be likely to change. With this paper what they did is just in six patients – so it’s very much in the realm of proof of concept – two with breast cancer, three with ovarian cancer and one with lung cancer, and they took blood samples from them as they went through treatment, and sequenced the DNA of every single gene and compared them to see what the difference was. This is something that only a few years ago would have been completely impossible, and is now getting into the realms of being done routinely in the NHS.”

Kat: “This is really important because it’s the kind of information you’d only get from a surgical biopsy – taking a little sample of a tumour and the tumours that have spread to elsewhere in the body. And that’s just completely practically not feasible.”

Henry. “That’s right. And of course everything we’ve discovered over the past year or so in terms of how tumours change, how different bits of the tumour are different from each other. The bits that are given off into the blood are from all different parts, so this is a way to get round that whole issue of intratumoural heterogeneity – the differences between the tumour and the metastases. And this is a way to get a snapshot of all the bits of tumour in the body to try and work out how they’re going to respond.

This is absolutely crucial because what it means is that doctors can start to try and get a handle on what sequence of treatments to give, whether resistance is coming up. In the lung cancer patient on this trial, they gave them a drug called gefitinib, which is a new generation targeted therapy targeted to a gene called the EGFR gene. The patient didn’t respond, but they were able to see this in the blood as it happens, as the mutation in the EGFR gene appeared in the blood. Just seeing that in real time is a huge step forward. It’s a potentially game-changing discovery.”

Kat: “Its’ certainly very exciting. As we said, it’s a very small study at the moment but I think this is going to become massive over the next few years certainly. Another area that’s really exciting is about trying to categorise different types of cancer, because we know that not all cancers are created equal – a couple of years ago our researchers put out a paper showing that there are at least ten different subtypes of breast cancer. So some of our scientists have put out a paper showing that there are three distinct types of bowel cancer at a genetic level.”

Henry: “I think this is quite interesting because previously they only thought they were tow, and they were quite similar to each other. But what was your sense of the implications of this paper? What happens next?”

Kat: “Two of the types of bowel cancer we k new about already, and one is this completely different sort that seems to grow from a different starting tissue.”

Henry: “This is the new one?”

Kat: “This is the new one – it’s something we haven’t really known about before, and there are really big implications, because knowing there’s this new type of cancer, that they seem to be very aggressive tumours, that they spread very fast, they’re resistant to some of the drugs we commonly use to treat bowel cancer. So knowing that there’s this new type out there that we should be looking for will help doctors maybe make decisions about how to treat patients.

And there are also some implications for research too, because currently the lab models that we used to study bowel cancer are based on the two types that we knew about. So we don’t really have good models for looking at this new type. There’s certainly a lot of work to be done by bowel cancer researchers.”

Henry: “I think it’s going to be fascinating to see how this kind of research pans out for other tumour types. You said we’ve got ten types of breast cancer now on a very detailed level. This is a slightly broader level but this is three types of bowel cancer. It will be fascinating to see over the next few years quite how detailed the picture can get. One researcher I spoke to recently said it’s like we used to have an A to Z map and now we’ve got Google Earth – we can really zoom in and see what’s going on with these different types of cancer.

Kat: “But, of course, the big challenge is to make it clinically relevant. It’s no good to tell a patient ‘You’ve got this type but unfortunately we don’t know how to treat it yet’”

Henry: “We need to get the treatments through to actually work out which treatments to give the patients.”

Kat: “And speaking of treatments, the Cancer Drugs Fund has been in the news as charities have raised concerns over future access to treatments for cancer patients when the dedicated fund closes next year, with no clear arrangements in place to replace it.  The government's £650m Cancer Drugs Fund has paid for treatment for some 28,000 patients in England since 2010, and is likely to be replaced by a scheme called “Value based pricing”, but exactly how this will work isn’t clear. To find out a bit more about this important area, I spoke to our head of policy development, Emma Greenwood.

Emma: “The Cancer Drugs Fund was first introduced in 2010, to meet the need for cancer patients to have better access to cancer drugs. So there was a sense in the research community and the clinicians that cancer patients weren’t always getting access to drugs as quickly as they could be. So it allows patients to get access to drugs while we’re awaiting a NICE [National Institute for Health and Care Excellence] decision, or if they’ve been turned down by NICE, actually the Cancer Drugs Fund will allow patients to have access by that route as well.  It’s about £200 million a year set aside to be allocated through the Cancer Drugs Fund. Obviously that doesn’t always mean that all of that gets spent, but that’s the kind of budget for it.

Kat: “Broadly, has it worked? Has it been a good thing and have patents had access to these treatments?”

Emma: “So broadly we get data on this every quarter and we think since its introduction it has made a difference. We know that it’s helped more than 28,000 cancer patients have access to drugs that they might not have otherwise had. And it certainly helps get speedier access while you are waiting for drugs to go through the NICE process. It’s been particularly helpful for treatments like abiraterone – the new prostate cancer drug that Cancer Research UK had an essential role in developing – which means that men with advanced prostate cancer were able to access abiraterone prior to NICE finishing its approval process, which is great.

Kat: “But as we’ve heard, the Cancer Drugs Fund is coming to an end next year. Do we know yet what’s going to replace it?”

Emma: “The Cancer Drugs Fund, when it was first introduced, was always going to be a temporary measure, and the reason for that was that the Government had already committed to looking holistically at its system for pricing drugs. They’re considering a new way of looking at pricing for drugs and negotiating those prices which is going to be called Value Based Pricing. So the Cancer Drugs Fund is due to close in March next year [2014], and what is meant to happen is that it will be rolled into this new system of Value Based Pricing. Now as yet we’ve not really had any data to look at the impact fo the fund above and beyond number of patients accessing the drugs, and we think it’s really important that that evidence is publishing to feed into the Government’s plans for Value Based Pricing. We really want to make sure that cancer patients don’t lose out when the fund does end. It is also really important to remember that cancer treatments can have serious side effects. So that needs to be balanced together with the benefits that this fund has brought, which is why we really do need a solid evidence base to make decisions.”

Kat: “The prices of cancer drugs seem to be getting higher and higher, and it’s a really big challenge. What’s Cancer Research UK doing to try and make sure that patients do have access to drugs and that they are affordable?”

Emma: “Obviously the Department of Health and the NHS have to really consider how they can find long-term sustainable ways to fund all types of cancer treatments. It’s not just about the cost of drugs, we have to take into consideration access to radiotherapy – particularly new innovative radiotherapy techniques – so there’s a real challenge there. I think that Cancer Research UK’s role has always been to ensure that these decisions are made with the best possible evidence base, that we’re really looking at the impact that these drugs, radiotherapy and surgery can have on patients. And part of it has to be challenging the pharmaceutical industry and saying that they have to act responsibly when it comes to the pricing of their drugs.”

Kat: “So there are some pretty important areas that Emma raises there, Henry.”

Henry: “Absolutely, and this has been one of the key issues, certainly in the media this has been a massive issue for the past few years. The Cancer Drugs Fund came along and defused the issue a lot, meaning that more patients are getting cancer drugs, but we need to know what’s happening next – we need to know what’s going to happen. Essentially, the Government needs to let us know that’s going on. They owe it to us, they owe it to the patients, particularly, to give them certainty in the future.”

Kat: “And another issue raised is the cost of the treatments, and this is now starting to become an issue more and more, certainly as we’re in a global recession, that maybe there is a role for the pharmaceutical companies to bring in fairer pricing for some of their treatments?”

Henry: “Absolutely. And it’s important that everyone works together – the NHS, the pharmaceutical industry, everyone – to work out how we get the best deal for patients. These new treatments are exciting, they work very well in a small subset of people. We need to work out how to get the right ones to the patients. They all come with tests that can be quite expensive, to find out those things. This is going to be a rethink in how we give treatment to cancer patients, we need to make sure we’re doing it right and that we can afford it. But it’s also important, as Emma said, that it’s very easy to get caught up in the blockbusting cancer drugs, but we can’t forget about surgery, which is so important in treating cancer patients, but also radiotherapy. There’s a lot of kit around the NHS that needs upgrading, and we need to make sure that the money is there to do that as well.”

Kat: “It’s certainly an issue that’s not going to go away any time soon. That’s the news for this month, thanks Henry.

April was Bowel Cancer Awareness month, so to find out more about the progress that’s been made in treating people with this type of cancer over the years – and the challenges that still lie ahead – our reporter Alan Worsley spoke to bowel cancer expert Professor Tim Maughan, who’s based at the Gray Institute in Oxford.”

Tim: “I think one of the most important things that’s happened in bowel cancer in the last five to ten years is the introduction of the screening programme. So that’s research from the 80s and 90s but that’s now really making a difference. And, when people get their little envelope through the post with that little thing they’ve got to put their poo on and send it back, it’s really important to do that because that gives us a chance to detect any things that are going to develop into bowel cancer before they get nasty. That enables us to nip it in the bud because prevention is better than cure.

The second thing I’d say is our understanding of the way bowel cancer comes in different types. So it’s not all one disease and there are different what we call molecular sub-types within bowel cancer. And the big effort at the moment is trying to work out what new treatments can work in one of the subtypes as distinct from another of the treatments and in that way we hope to improve treatment for everybody in the end.”

Alan: “Now you mentioned bowel screening. What’s so important about this and what do you hope it will accomplish?”

Tim: “What we know about cancer is that it takes maybe a decade or even longer to grow from the first changes in the cell to a full-blown cancer. And, in the bowel, that’s a place we can get at through colonoscopy – a magic eye up the back passage – and that means we can remove a polyp, which is the way it begins, before it has become cancerous. We can see it on colonoscopy and we can remove it.

Now what the bowel screening programme does, when you get the kit through the post, that’s looking for the little trace of blood that might be there hiding in your stool which you can’t see. And, if it’s there, you go forward for a colonoscopy and 70 per cent of people who have a colonoscopy have got something wrong with their colon. So that’s really important. It means that if you get the call to go for a colonoscopy then go for it! Because actually that’s a really important thing to pick up those early steps of bowel cancer and hopefully detect it before it’s going to be at risk of actually spreading and killing.”

Alan: “There’s a lot of research now into what different sub-types of bowel cancer require different chemotherapy. Why don’t we have one drug that can hit all bowel cancer? Why do we need to specify what type?”

Tim: “Well perhaps I can use the analogy of a car: when you take your car to the garage to get it fixed, it’s not always the same solution. It depends on what the problem is. In a cancer cell, imagine you’ve got an accelerator cable and you’ve got a pedal which you press on and then you’ve got the links down to the engine. Now one of the important pathways as we call them in cancer, is a bit like an accelerator cable. The pedal we call the epidermal growth factor receptor and we’ve got drugs that act a bit like taking your foot off the pedal.

But one of the common mistakes that happens in the development of bowel cancer is a mutation in the gene called the KRAS gene. Now that’s kind of like two steps down the chain below the pedal. So if you take your foot off the pedal but you’ve got a fault in the accelerator cable that’s keeping the engine going, taking your foot off the pedal isn’t going to do anything – the engine is still going to be racing. So that’s why KRAS gene mutation defines patients in whom these sorts of drugs don’t work because the particular mistake that has happened in their cancer means that that approach to therapy cannot work.

So that’s just one example of the way a particular molecular change has a direct effect on the way a treatment does or doesn’t work. So when we take that example wider, what we’ve found in bowel cancer is that by doing some specific tests we can sub-divide it into four or five sub-types.”

Alan: “What other research into therapies do we have?”

Tim: “Major treatment, apart from surgery, is radiotherapy and there’s been a fantastic renaissance in radiotherapy. Radiotherapy is the use of ionising radiation to treat cancer. That’s a bit of a technical term but think of it as a molecular snooker cue. So a snooker cue knocks a ball out of the way and what ionising radiation does is it knocks an electron out of orbit. Now electrons like to go round in pairs and if you knock one of them out you have an unpaired electron. Any chemist will know that an unpaired electron is called a ‘free radical’ and, if it also carries a charge, then we call it an ‘ion radical’. And that’s about the most reactive thing that ever happens anywhere and it will react with whatever’s next to it instantaneously.

So in the cell, when you’re using radiotherapy, you form these ion radicals and they react. And, most importantly, they react with DNA. So these ion radicals are able to interact with DNA and break the DNA and that’s something that a cell finds really difficult to deal with. Remember that cancer is a disease of DNA. So in a cancer cell the DNA has gone wrong and also the repair mechanisms of DNA have gone wrong very often as well. So radiotherapy targets the DNA in a very precise way, and in a very powerful way, but also in a way that can be physically localised to the cancer. So it’s not going everywhere all over the body like a drug does.

Radiotherapy is a fundamentally important approach because it targets the heart of what’s gone wrong with cancer. The second thing, and why there’s been a renaissance in radiotherapy, is because of computing and engineering that have enabled us to target that radiation very precisely – with millimetre accuracy – to where the cancer is. So, instead of it going all over the place, we can really target the cancer and deliver that DNA damaging treatment exactly where we want it.”

That was Professor Tim Maughan talking to Alan Worsley.

And finally, it’s time for our heroes and zeros. We have tens of thousands of heroes this month – that’s everyone who’s participated in our first Citizen Science project, Cellslider. Together, they’ve classified more than a million cells in breast cancer samples, slashing the time needed for this kind of analysis from 18 months to just three. You can get in on the act and help us hit our next million at Cellslider.net.

And our zero of the month is Japan Tobacco International, who’ve yet again been slapped down by the Advertising Standards Authority, who ruled that their recent newspaper ads focusing on black-market tobacco were misleading and unsubstantiated. In fact, as figures show, the black market in tobacco certainly isn’t ‘booming’ in the UK. The illicit market for cigarettes has more than halved in a decade, and JTI itself has acknowledged that the illicit trade in tobacco has reportedly been a declining trend in the last 10 years.

This isn’t surprising news – a recent survey showed that almost two thirds of the public don’t trust the tobacco industry to make believable and independent arguments about how to reduce smoking rates. The government is currently considering the evidence for introducing standardised packaging for tobacco in the UK – it’s a move we want to see, and it would strip slick, glitzy branding from packs and give children one less reason to start smoking.  We’re eagerly waiting for what we hope will be the right decision.

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 podcast@cancer.org.uk, 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.