Spotting cancer early, new ovarian cancer gene and a childhood cancer trial

Cancer Research UK
We investigate a dye that spots early signs of oesophageal cancer, a new ovarian cancer gene, and a clinical trial to treat childhood leukaemia.

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This month - dye spots early signs of oesophageal cancer, prostate cancer drug rejected by NICE, faulty gene linked to better ovarian cancer survival, new drug trial to treat childhood leukaemia, and finally, we speak to our chief executive Dr Harpal Kumar as Cancer Research UK celebrates its tenth birthday.

Transcript

Welcome to the Cancer Research UK podcast. I’m Ailsa Stevens.

A fluorescent dye that can be sprayed onto the oesophagus – or food pipe – could be used to detect oesophageal cancer earlier and spare patients unnecessary treatment.

The research, funded by the Medical Research Council and Cancer Research UK, studied samples of a particular type of oesophageal cancer called adenocarcinoma.

Before this disease develops there is a detectable pre-cancerous stage called Barrett’s oesophagus, which can be easily treated successfully. Rates of oesophageal cancer are rising rapidly, so early detection could save many lives.

When sprayed onto the oesophagus , the dye attaches to normal, healthy, cells but is unable to stick to cancer cells or those in the early stages of turning cancerous. This gives doctors a clear signpost to where the disease is developing.

Professor Kevin Brindle, one of the study researchers based at Cancer Research UK’s Cambridge Research Institute, tells us the potential benefits of this new test.

“What we've developed is a targeted imaging agent which is just a plant lectin – you get it in brown bread, for example – conjugated that to a fluorescent dye, and you can simply spray it onto the surface of the tissue. It shows negative contrast, so it doesn't bind in regions of dysplasia.

What that means is that when you look at the fluorescent image, you get sort of holes in the image, and then you simply biopsy those holes so you get real-time validation of your imaging readout. So it's a way of finding these small early-stage lesions very quickly.

Obviously the next step is to do this in patients and we're currently discussing the best way forward to do that. We need to get the material approved for clinical use, manufactured under GMP for example, and those are the issues we're dealing with right now.”

Abiraterone, a drug that that could improve survival from advanced prostate cancer, has been rejected on grounds of cost in an initial review by NICE – the government watchdog responsible for recommending new drugs.

Cancer Research UK funded some of the early stage development of abiraterone – which was made available in the UK in September last year.

Professor Peter Johnson, Cancer Research UK’s chief clinician tells us why this decision is disappointing.

“Abiraterone is a very promising drug which is able to help men with prostate cancer that has come back after they've had chemotherapy. We're very proud of it because it was developed with Cancer Research UK's support in this country.

What we're disappointed about is that so far we haven't got to a position where it can be made routinely available in the National Health Service, partly because it's priced too expensively by the manufacturer, and partly because NICE has taken a rather narrow about what drugs qualify for it's so-called “end of life” criteria.

What we need to try and do is find a solution for making abiraterone routinely available in the National Health Service, We already know that it's very effective drug from the clinical trials that have been carried out, and because more and more patients are receiving it from the cancer drugs fund already. It's popular with men, it's popular with doctors. What we need to do is try and find a way to get the price right so the National Health Service can regard it as good value for money.”

Ovarian cancer patients who carry faults in the BRCA1 or BRCA2 genes are significantly more likely to survive the disease than women without these faulty genes, according to new research from Cancer Research UK scientists in Cambridge.

The researchers suspect that the gene fault is affecting the underlying biology of the cancer cells, making them more susceptible to the effects of chemotherapy.

Dr James Brenton, our ovarian cancer expert, explains the implications of the findings

“I think these have very, very important implications for women with ovarian cancer. The first thing to say is that of course, we've previously viewed being tested for BRCA1 and BRCA2 as a negative thing, because there wasn't anything that could practically be done about the result, except perhaps the opportunity of reducing your risk of breast or ovarian cancer by having surgery.

But what this result says is that if you are unlucky enough to have a BRCA1 or BRCA2 mutation or fault you've inherited from you're parents, you're likely to do better and to live longer than other patients with ovarian cancer, so that's of a practical use.

The second thing is that what this result probably means is that the response to chemotherapy is probably better in patients with BRCA1 and BRCA2 faulty genes because the way that the drugs are interacting with the way the cancer repairs DNA inside the cells means the cancer's more vulnerable and more susceptible. So other new therapies – particularly the PARP inhibitors – may now be used more widely if we know the [BRCA] status of every woman with high-grade serous ovarian cancer (the particular type that is associated with these faults).

I think there's one other really important thing which is that over time, we'll reduce and prevent high-grade serous ovarian cancer because we can offer testing to other family members who can then take adaptive measures to stop this disease occurring by either surgical or other interventions that may reduce risk.”

Cancer Research UK’s Drug Development Office has opened the first trial of a new drug to treat children with acute leukaemia, whose cancer is no longer responding to treatment.

Project leader Dr Shamim Kazmi-Stokes tells us why this is an important step forward.

“Despite great progress in the treatment of childhood leukaemia, leukaemia that has returned or is resistant to current treatments remains one of the key causes of death from childhood cancer.

This drug belongs to a new class of agents called aurora kinase inhibitors. This agent looks promising in laboratory studies so far, and this particular trial will assist in establishing the correct drug dose and investigate if it can treat children and adolescents with leukaemia.”

As Cancer Research UK celebrates its tenth birthday this month, our reporter Angela Balakrishnan spoke to the charity’s chief executive Dr Harpal Kumar about his highlights, how far we’ve come and the challenges we face ahead.

Angela Balakrishnan: Hi Harpal, thanks for chatting to us. Earlier this month Cancer Research UK celebrated its tenth birthday. What do you think have been the most significant milestones?

Harpal Kumar: Well I think perhaps the thing that feels most significant to me, probably the most important thing to me, is the fact that survival rates continue to improve year on year. If anything, there is a sense that we're seeing an acceleration in the rate of improvement in survival from cancer, and that of course means many, many more people are surviving every year than would have done the previous year, and especially than ten years ago. And so that continued progress in terms of what we are here to do – which is to help more people survive cancer – is great, and is something to really celebrate.

Now, of course, there's a huge number of things that have contributed to that – we have a whole suite of new treatments, whether they be new drugs (and there are many of those that we could talk about that have emerged over the last ten years), whether we talk about new ways of delivering radiotherapy that are much, much kinder to patients but just as effective as previous versions were. We have new screening tests which mean that in years to come we're going to see much better survival from cancer. So a whole range of things that have happened over the last ten years.

AB: And looking ahead to this year, what are you most excited about?

HK: Again, there are lots of things that are going to be happening. There are some very exciting new drugs in the pipeline. We're very hopeful that some of them will make it through in terms of proving in clinical trials that they really are effective.

For example, there are some very exciting new drugs for lung cancer, and many people will know that lung cancer is an area where we've made relatively little progress over the previous few decades, and it's an area we need to make progress in. So I'm hopeful that we'll see some real progress in that area over the coming year.

Many people will know that we've launched what we call our Stratified Medicine Programme. This is an attempt to really think about the future of cancer treatment, and the next year is really going to be a pivotal year in figuring out how we're going to make this real, in terms of giving patients the mechanism by which they're going to receive a much more personalised treatment journey in the future.

AB: We've heard a lot about Cancer Research UK's investment into personalised medicine, Why do you believe that this tailored approach to treatment is the way forward, and when do you think that this sort of research will actually change the way patients are treated?

HK: The most important principle that underlies personalised, or stratified, medicine – whichever term we want to use – is that we know that we're all different as individuals. We know that despite the fact that our DNA is very, very similar from one person to the next, nevertheless, we look differently, we think differently, we act differently, we behave differently. And so why should we expect that a treatment given to one person is going to be processed by the body in exactly the same way to the next person?

The reality is, of course, that it doesn't happen that way. So the reality is that we know for most cancer treatments, they only work for a small proportion of the patients to whom they're given. For example, it may be for one drug that it will only work for 20 per cent of the patients it's given to.

Which means that for that 20 per cent, great, they get the benefit. But for the other 80 per cent, they suffer the side effects of those treatments, and it also means that they're not getting a treatment that might work for them during that period when they're getting the treatment that won't work for them.

So the whole principle of this is to figure out for each individual what's going to work, and - just as importantly – what isn't going to work, so that we can really target for each patient what's going to be most effective.

What's changed is that we now have the technology to do this. And there's a whole suite of technologies that are enabling us to do this, and - just as importantly – those technologies are now affordable. So we can start to make this real for people in a way we couldn't even two years ago. We can determine for any individual patient what's going to work, or rather what's most likely to work, and given them that in a way we couldn't have a few years ago.

You ask when is this going to really happen? In many ways it's happening already. If we look at a drug like Herceptin, a drug that we've had a huge involvement in over the years, we know that it only works for roughly 20 per cent of breast cancer patients. And actually, we already have a test that determines which is that 20 per cent. So there is an example of a drug that we're already using in a very personalised way.

There's a new skin cancer drug that's emerged over the last year where again, we know the test we need to use to determine which patients should get it and which shouldn't. So it's starting to happen already, but we're really going to see an explosion over the next five years or so.

AB: Another exciting project is the Francis Crick Institute. What impact do you think this is going to have on medical research in the UK?

HK: I think the Francis Crick Institute is important for probably two different sets of reasons, actually. One set of things is the science in and of itself that it will be doing, which we believe will be the very best science in the world. And it's that science that gives us the understanding that enables us to develop new treatments.

I talked about Herceptin just a few minutes ago – Herceptin is an example of a drug that was based on a discovery made in our London Research Institute twenty years or so ago. That was found to be a pivotal process that goes wrong in many cancers, and subsequently a drug was developed to address that mistake that occurs. We need to be constantly doing that kind of research to figure out which are the pathways that go wrong, that we need to address through new treatments.

What the Francis Crick Institute will do is enable us to do much more of that research much more quickly and in a much more effective way, in the sense that it will bring different scientists working from different angles towards the same problems. But there's something else that's really important – I said there were two things. And the second thing is really about the whole way we do science, and that is to say that increasingly we know that we have to look in a much more cross-disciplinary way about science.

It isn't sufficient any more to put a bunch of biological scientists in a room and expect them to come up with all the answers. We know that if we want to come up with the answers we've got to mix biologists with chemists, with mathematicians, with computer scientists and so on. But it will also be training a new generation of scientists [and] doctors, who will have been brought up in that new culture, will have been brought up in that new way of doing science. And so those people can then go out and take that new way of doing science out to wherever it is they go thereafter.

AB: Something that you touched upon in your first question about survival rates - now we know that breast and bowel cancer are the most common cancers in the UK. Survival from those cancers has doubled over the last forty years – in part that's down to new drugs, better surgery and radiotherapy and faster diagnosis, which screening has played a big role in. Do you think screening has a bigger role to play in our fight against cancer?

HK: I think screening does have a bigger role to play, but in order for it to play that role we need to develop better screening tests. We have some good ones now, but we don't have enough. If I can just broaden this question our a bit more, we absolutely know that earlier diagnosis has a much bigger role to play in the fight against cancer.

We know that if we catch cancers late we're much less able to treat them successfully than if we catch them early. And we also know that the complexity of treatment gets ever greater the more advanced a cancer is. So the earlier we can diagnose the better.

Screening is one way of getting an early diagnosis – it's not the only way, but it is one way of getting an early diagnosis. But the point is because screening is something that you do for a whole population, or indeed an age-group within a whole population, it has to absolutely be right. And as I touched on, other than in a few areas – bowel, breast, cervical – we don't yet have good enough quality tests that warrant a national screening programme. But we're working on them.

We're looking at a number of new tests in different cancers where we believe that there is a opportunity, where there is some reason to believe something might be successful. But until we've done the work, we don't have those. We're looking at lung cancer, we're looking at pancreas, we're looking at ovarian cancer, we're looking at oesophageal cancer – those are just some of the ones where we have programmes currently under way.

AB: Radiotherapy is another factor that's contributed to improving survival, and we know that it's changed dramatically over the last 100 years, and the treatment helps cure more patients than chemotherapy. Cancer Research UK has said that patients are missing out on radiotherapy, so what do you want to see happen to improve people accessing these world-class services?

HK: Cancer Research UK has been very vocal in expressing concerns about the state of radiotherapy in the last few years, and the good news is that lots has happened in response to that. Most notably, there's been a huge investment in radiotherapy machines across the country – looking back 5 or 10 years we had a real deficit in just the number of machines that were available. So at least that's something that's being addressed.

The next big problem that needs to be addressed is the number of people delivering that radiotherapy. At the moment there are two particular categories of people who are important to the radiotherapy process – medical physicists and radiographers – and we don't have enough of them at the moment. We have enough to deliver the more conventional forms of radiotherapy, but some of the newer forms of radiotherapy are heavier in the demands on those two categories of people I've just talked about, so we need more of them.

That's an area that we'll continue to push on – we'll push on the government to make sure that these workforce issues are addressed. Because, actually, once we've done that we have the machines, we have the capability to really make a step-change in our use of the more modern forms of radiotherapy which are much kinder for patients and just as effective.

AB: AS a charity Cancer Research UK has made some amazing progress in tobacco control – there's been our Smoke-free and Out of Sight, Out Of Mind campaigns. Our next step is campaigning for plain packaging on cigarettes. Why do you think that removing all branding on tobacco products will affect smoking rates?

HK: What we absolutely know is that the tobacco companies will use whatever means they have at their disposal to encourage people to continue smoking – to make it something that feels exciting, trendy, something that they want to do. And that's what marketing does – it's a mechanism by which the company persuades you as the consumer to take part in the produce they're offering.

Now what we know is that over the years the tools that are available to tobacco companies are gradually being whittled away. They can't advertise any more, we're going to get rid of displays ins hops, we've got rid of vending machines. Really, the only tool that's available to tobacco companies now is the packaging, and what we've seen starting to happen over the last few years is more and more sophisticated design of packaging for cigarettes that is very clearly targeted at appealing particularly to younger people, to make smoking look trendy, to make it look exciting, and thereby to hook people in.

And that's why we believe that if we can address the packaging issue, it removes a further tool that the tobacco companies have to get people onto this habit that they then find very difficult to break. We have to address this because we know that it remains, by an order of magnitude, the single biggest cause of cancer, and therefore the single biggest cause of cancer death.

AB: We're up against a big fight with the tobacco companies, and cynics might say this isn't going to have an impact. What would you say to them?

HK:It absolutely will have an impact if it's implemented, there's no question about that. Companies would not invest the sums of money that they do – and this isn't just in the tobacco industry but across all industries – if they didn't believe it had an impact. It's really as simple as that.

AB: What other challenges does Cancer Research UK face in the coming years?

HK: We've talked about some of them – we've talked about the fact that early diagnosis is a really big priority, but it's also a really challenging priority, as is personalised medicine. This is difficult stuff to get right, and we have to get it right, but the prize is great if we do so.

I think one of the big challenges Cancer Research UK faces is that our ambition, our desire to make faster progress, is constantly limited by the funds we have available to us to do so. There is so much more we'd like to do every year, but we're stymied by our ability to raise more funds. I think that's a challenge for us.

AB: So for the next ten years for Cancer Research UK, where do you think we're going to be within cancer research? What would you like to have seen happen?

HK: I'll finish where I started in that the most important thing will be many more people surviving cancer, and that will be the true test of the progress I would like us to have made over the next ten years, particularly in some of those harder-to-treat cancers. Yes we've made great progress in bowel and breast and some other cancers, and we want to continue to make more progress in those cancers. But I'd really like over the next ten years for us to be able to see a discernible improvement in lung cancer, in pancreas cancer, in oesophageal cancer – in some of those areas where we've made relatively little progress.

We know that science has the power to change the lives of so many people, and we've seen this over the last ten years and the decades before that. There's no doubt in my mind we'll see this again over the next ten years, and nowhere will this be more true than in health. It's up to us to make sure that that progress is an manifest in cancer as it is in any other area, if not more so.

AB: And a final question – what motivated you to start working in this field, and what continues to make you want to come into work every day?

HK: I love being in an organisation where there's progress being made. We have that in spades at Cancer Research UK and huge progress is being made in cancer. But I also like being in an organisation where there's real challenge, and personally that's what stimulates me.

And there is real challenge in cancer – it is incredibly complex, really tough problems that we have to crack, but the joy of cracking them is immense and the benefit to society is immense. That's more than enough to keep me happy.

We’ll be back next month with all the latest news and features. In the meantime, you can keep up to date with our Science blog.