Read our update on the Stratified Medicine programme

In the not-too-distant future, most people treated for cancer (and many other diseases) will have some sort of genetic test performed on their cancer, to help their doctor decide which treatments are likely to work best. In fact, this ‘genetic revolution’ in medicine is already underway, and some hospitals already offer these tests when appropriate.

But this isn’t standardised across the health service – testing methods vary from centre to centre, and not everyone has access. On top of this, samples often have to be sent from one centre to another for testing, and the requests and results are often paper forms, meaning data has to be re-entered and can’t be automatically checked.

Clearly, this situation needs to change, and quickly. New ‘genetically targeted’ drugs are becoming available that can help patients whose cancers contain certain gene mutations, such as vemurafenib, which targets mutations in the BRAF gene, and which is licensed to treat people with melanoma.

So, in June 2010, we decided to lead the charge in preparing the UK’s NHS for this forthcoming era of genetic medicine. We put together an £18 million partnership – between the government, the NHS, pharma companies and ourselves – to streamline and standardise genetic testing of tumour samples across the UK’s health service.

The result was the Cancer Research UK Stratified Medicine programme, which enrolled its first patient just 18 months later. For full details of how the programme works in practice, read this blog post or watch the accompanying video.

But there have been several exciting developments in the six months since the first patient signed their consent form, so we thought it was time for an update.

Number of patients tested

By the end of April 2012, 2,622 patients had volunteered to take part in the programme, and so far, 815 sets of cancer gene test results have been analysed and returned to the patients’ doctors. 95 per cent of all patients approached to take part have agreed.

Although these gene tests are more a proof-of-concept than to guide active treatment, we’re now building up a sizable database of clinical and genetic data on patients’ tumours that’s set to become a valuable resource for UK researchers.

New clinical trials launched

As a direct result of this programme, we’re delighted that two pharmaceutical companies are looking to open new trials in the UK, drawing on data from the Stratified Medicine programme.

Roche will be testing their drug vemurafenib (licensed for melanoma with BRAF gene mutations) in patients with other forms of cancer, which also have the same BRAF mutations. And Bristol-Myers Squibb are seeking regulatory approval for another trial.

This is fantastic news, and shows how – as well as making new, promising drugs available to UK cancer patients – investing in NHS infrastructure encourages further economic investment from industry. This is particularly important given the UK’s current financial situation.

And – even more important – a healthy research environment underpins  improvements in treatment and survival.

Cutting edge IT infrastructure

We’re also working with software giant Oracle, along with our Informatics Advisory Board of data experts, to improve the way data from the programme can be analysed.

As a result, we’ll be using Oracle Health Sciences Translational Research Center to further refine the way we and our partners can use the Stratified Medicine data.

International expertise

And finally, we’re now helping organisations in other countries to set up similar programmes. We’ve been sharing what we’ve learnt so far with senior staff from the Australian, French and Norwegian health services, and are in preliminary discussions with other countries too.

It’s a source of huge pride to us here at Cancer Research UK that this initiative is being seen as one of the best in the world – and our Stratified Medicines team have been invited to present their work to one of the biggest events in the cancer research calendar: the American Society of Clinical Oncology’s annual conference. We wish them well on their trip across the pond.

Jean King is a pioneer of tobacco control policy.

It’s World No Tobacco Day, focusing this year on the need to expose and counter the tobacco industry’s “brazen and increasingly aggressive attempts to undermine global tobacco control efforts”.

To acknowledge this, the World Health Organisation is celebrating some of the people who’ve made outstanding contributions to tobacco control. We’re thrilled that one of these is Jean King, Cancer Research UK’s tireless Director of Tobacco Control, for her work in combating the tobacco industry’s interference in public health.

Together with her colleagues, Jean’s made huge strides over the past two decades. For example, she developed Cancer Research UK’s code of practice on tobacco industry funding, stopping scientists who get money from these companies from receiving research funding from us.

She was also instrumental in our campaigning for the tobacco advertising ban in the 1990s, smoke-free legislation in the 2000s, and the recent ban on vending machines and shop displays.

Jean also set up and still runs the Cancer Research UK Tobacco Advisory Group, enabling us to support scientific research into tobacco control. And her reach spreads much further than the UK – together with the American Cancer Society, she set up the Framework Convention on Tobacco Control Awards and the Africa Tobacco Control Regional Initiative. She also helped to establish the EU Smokefree Partnership, pushing for strong tobacco policies within Europe.

We spoke to Jean to find out more about what she’s achieved over the years, what motivates her, and why tobacco control is such a vital part of our efforts to beat cancer.

Let’s go right back – when did you first start working in tobacco control?

About 20 years ago Cancer Research UK’s predecessor The Cancer Research Campaign had an education research committee that used to fund some tobacco work, and we gradually got involved in policy work through ASH and at the European level.

Altogether I’ve worked here for 23 years. I’m not sure I thought I’d be staying that long when I started, but my job has changed and got more and more interesting so it’s been a great journey.

What drives you to do tobacco control work? There may be easier or smaller targets, so what gets you out of bed in the morning?

I think people get absolutely immersed in the issues around tobacco and tobacco control. Before it was my main focus of work I used to think people were a bit obsessive, but as you get more and more into it, it takes you over.

It’s not just a health problem that is entirely preventable and is killing millions of people in very horrible ways, especially in those parts of the world where there isn’t good treatment, but there’s the David and Goliath thing. There’s this opposing force that’s trying to keep people addicted to something that’s going to kill them, just to make money.

You do become a bit adversarial, definitely. It makes you feel that you’ve got to stand up for children, for the next generation – we don’t want them to get hooked – so it gets very absorbing.

Tell me about some of the things you’ve done over the years working for Cancer Research UK in tobacco control?

We’ve had campaigns and expert meetings, we’ve funded different bits of independent research, and we’ve had to really pull out all the stops to try and get studies published in time so that we could use them in talking to government at critical times in parliamentary debates.

We’ve supported groups and independent studies that have been amazing in what they’ve produced and shown, and we’ve set up the Smoke-free Partnership in Europe, the Tobacco Advisory Group. The charity has had a lot of foresight in recognising that we need to have dedicated funding for showing the evidence that we need, and seeing where there are gaps and seeking to fill them, so we can present a very strong case on what policies are needed to cut smoking rates.

What are you most proud of, looking back at this point?

Probably the Framework Convention on Tobacco control, and the fact that we were able to contribute to that, to support people who were working for that around the world before there was any significant funding in international tobacco control.

Together with the American Cancer Society we were supporting small grants so that people could get things off the ground in parts of the world where there was very little control on tobacco companies. Seeing this public health treaty, the Framework Convention, come together was incredible – if we could implement that fully we could knock the tobacco epidemic on the head. We could literally be saving millions of lives. That’s amazing.

Then as well, there’s the work I’ve been describing about the charity opposing the tobacco industry, and I think that‘s great. It’s a huge honour that the WHO has recognised that work.

If it’s possible to pick one, what’s the most scandalous thing that you have seen the tobacco industry do?

There are so many, such as denying the harmfulness and denying the addiction, when their own documents show that they were actually trying to enhance the addictiveness of tobacco.

I’ll give you a story that illustrates it all that a colleague in Nigeria told us. There were parties sponsored by a tobacco company, targeted at young people, where not only were you given a cigarette when you went in the door but you were told to light it up.

As far as I’m concerned, that’s the equivalent of giving someone a loaded syringe, I just think it’s outrageous. And these are the sorts of things that tobacco companies are doing around the world that we need to stop.

Have you ever smoked?

I did! I was lucky that I started later than most people do – I was probably about 19 or so – and I managed to stop within about five years. There was a group of us at college together and we all stopped.

I fell again when I was living abroad. I was on a long journey with people who were smoking, and I just took a couple of puffs because it was a boring journey and I couldn’t believe it – I was back on ten or 20 a day for a few months. That was a long time ago now, and happily I’ve been free from cigarettes since then.

Working for a cancer charity, we see all the time the devastation that smoking causes – do you have any personal experience of the kind of damage that smoking causes to people and to families?

I know people who’ve died from lung cancer as smokers, people with respiratory illness as a result of smoking and I have a close friend who I think is in denial about a condition that she has which is very debilitating, but was definitely (in my view) caused by her smoking.

I think it’s all around us and I’m always amazed that the tobacco industry spokespeople can be so flippant about that, because I think most people hearing them will know somebody who’s been touched by it.

One of the injustices that we need to try and address is around the families of smokers who die.  - Because there’s this mistaken idea that smokers brought it on themselves, then people don’t express the outrage that we should be expressing towards the tobacco industry. It’s not a question of bringing it on yourself – most smokers start as children, it’s highly addictive and they are marketed to, so people should get over that idea. I’d love us to have a sense of outrage about all this suffering that’s being caused.

Historically it’s crazy, and I believe that in a couple of generations from now people will look back and wonder what on earth was going on. People do say it should be banned, but it’s not practical as there are so many people still addicted in this country. And also you don’t want to make it more glamorous than some young people find it already.

We have a pretty good idea about how we could get the smoking rates down so that smoking becomes something that is so rare that we are virtually tobacco-free, and that’s what we want to aim for. For a start, we’ve got one in five adults smoking but two-thirds of those want to stop, so if we can find better ways to help them stop and prevent young people starting – which we’re trying to do by getting cigarettes out of sight and into plain packs – all of these things together will drive the smoking rates down.

Some people ask why Cancer Research UK is campaigning so hard on tobacco -  why should we be doing this campaigning work?

Our aim is to beat cancer and over a quarter of all cancer deaths are caused by tobacco. So we could wipe out so much of the cancer toll simply by getting the smoking rates down, preventing young people from starting and helping smokers to quit.

Absolutely we need to be looking for new treatments for cancer, but at the same time if we can prevent so many thousands of cancers and deaths, then that has to be part of what we do to beat cancer.

Kat

Help us fight against the tobacco industry using glitzy pack designs that are attractive to children – join our campaign, The Answer Is Plain, now. 

A simple blood test might one day help doctors monitor the genetic changes in cancer in 'real time'

Over recent months we’ve written about exciting new research looking at how the genetic makeup of an individual patient’s cancer shifts and evolves as the disease develops and spreads.

At the moment the only way to monitor this is to take a sample of a tumour (called a biopsy) and test it in the lab. But this approach isn’t perfect – for a start, a doctor needs to be able to reach a tumour in order to take a biopsy, which often has to be done surgically. And monitoring the disease over time means repeated biopsies, which may need to be taken from multiple places if the cancer has spread.

Wouldn’t it be fantastic if there was a simple blood test that could reveal the genetic fingerprints of a tumour, no matter where it’s located in the body?

This solution may be closer than you think. Although it’s still at an early stage and needs more work, scientists at our Cambridge Research Institute have developed a blood test that can detect genetic mutations in tiny fragments of DNA shed into the bloodstream by dying cancer cells. And it has the potential to be a game-changer for the way the disease is monitored and treated – and maybe even diagnosed – in the future.

Here’s a short video of study leaders Dr Nitzan Rosenfeld and Dr James Brenton, explaining more about their exciting research and what it might mean for cancer patients in the future.

The Cambridge team has just published their results in the journal Science Translational Medicine, so let’s look in a bit more detail about how the test works and where this research might take us in the future.

What did they do?

When cancer cells die – either as a result of chemotherapy or radiotherapy, or due to ‘natural causes’ – they shed tiny fragments of their DNA into the bloodstream known as circulating tumour DNA (ctDNA). But because cancer cells usually have many genetic changes compared to healthy cells, some of these ctDNA fragments will be very different from the corresponding DNA sequence in healthy cells.

Although scientists have been aware of the existence of ctDNA for several years, it’s not been easy to analyse in great detail. The tumour DNA fragments are very small – only around 150 ‘letters’ (basepairs) long – and levels in the bloodstream are relatively low. But by combining some of the latest technology, the researchers developed a way of analysing ctDNA from just a couple of millilitres of blood.

To look at gene faults in ctDNA, the researchers first made multiple copies of all the DNA fragments present using a technique called PCR - a bit like taking multiple photocopies of all the pages in a recipe book. Next, they made copies of these copies, but focusing on specific genes known to be involved in cancer and tagging each of them with a clever molecular ‘barcode’ – to use our book analogy, it’s like making further copies of specific recipes while ignoring the rest.

Finally, the researchers read (sequenced) the DNA letters in each of these copied genes, looking for critical faults – analogous to reading through each individual photocopied recipe and searching for typos.

What did they find?

Before they looked at ctDNA, the researchers tested their new technique, called TAm-Seq, to look at six genes implicated in cancer in stored samples of ovarian tumours. Samples like this are normally quite degraded, and the DNA is broken into small fragments similar to those found in ctDNA. The researchers found that they could consistently get good quality data with very few mistakes.

Next, they went on to test whether the technique worked on ctDNA using a ‘mock’ sample created by mixing plasma from healthy volunteers (plasma is the fluid left over from blood when red and white blood cells are removed, and contains the ctDNA). When that worked, the team went on to look at more than 60 plasma samples from nearly 40 women with an aggressive form of ovarian cancer, and could pick up key gene faults in ctDNA with a high degree of accuracy.

Importantly, the team detected a fault in the EGFR gene in a sample from a woman whose cancer had come back after treatment but that wasn’t present in her original tumour biopsy. This shows that the technique might be useful for monitoring how tumours evolve over time, picking up new gene faults as they become resistant to drugs or radiotherapy.

Next, the researchers also measured how the levels of certain faulty genes present in ctDNA fluctuated over time in two women who were being treated for advanced ovarian cancer and one breast cancer patient.

Impressively, their technique could detect a drop in the relative proportions of faulty DNA following chemotherapy, showing that the number of cancer cells in the body had dropped. But the proportion of faulty ctDNA began to rise again once they stopped treatment, revealing that the cancer was growing again.

Finally, the team used TAm-Seq to look at samples from a woman who’d developed both ovarian and bowel cancer. She had surgery to remove both tumours at the same time, but five years later found a lump in her tummy. For various reasons, it wasn’t possible to do a surgical biopsy to find out whether this was the return of the ovarian or the bowel cancer.

The researchers tested her ctDNA, and discovered that it bore the same gene faults as her original ovarian cancer, but not the original bowel tumour. Fortunately for the woman, her doctors had already started her on a course of ovarian cancer chemotherapy, based on other factors, but had this test been available at the time it would have clearly helped their decision.

How could this be useful?

One of the biggest challenges we face in treating cancer effectively is the fact that tumours evolve and change over time, picking up new faults in their genes as they spread through the body and become resistant to treatment.

And as we discussed in our posts about recent research from Professors Charles Swanton and Mike Stratton, the discovery that the genetic fingerprint of tumours change over time within an individual patient raises big questions about how to pick the most appropriate drugs from the growing arsenal of targeted treatments.

At the moment, there isn’t a good way to monitor these genetic changes, except through repeated, invasive biopsies. So if this blood test lives up to its initial promise, then it could provide a simple way to help doctors analyse what’s actually going on within a patient’s body.

Not only would that help doctors pick the most appropriate treatment, based on the genetic signatures they find, but it could also be a quick way to see whether that therapy is working. And it could also be a useful tool to help researchers select patients for clinical trials of brand new agents that target specific gene faults in cancer cells.

At the moment this test just looks at a relatively small panel of specific genes known to be involved in different types of cancer. But advances in technology – along with the heaps of data being generated by large-scale cancer sequencing projects such as ICGC – mean that maybe one day it’ll be possible for doctors to sequence all the cancer genes in a patient’s ctDNA on a regular basis and use this as the basis for ‘real time’ decisions on treatment.

That’s a truly mind-blowing prospect.

There’s also the possibility that the test could be used as a screening tool, picking up genetic changes at the very earliest stages of disease when the chances of survival are much greater. But this would need to go hand-in-hand with imaging technology to ensure that a tumour can be found wherever it is lurking in the body, so the most appropriate treatment can be given.

What’s next?

Before we get too excited, there are some important limitations to be aware of. Firstly, the test isn’t perfect. Although it’s good at picking up DNA typos analogous to spelling mistakes or missing words and paragraphs, it’s bad at detecting particular gene faults known as amplifications. These happen when a gene is duplicated many times, often in ‘driver’ genes that fuel the growth of cancer.

Of course, the technique now needs to be tested in much larger numbers of patients to make sure it can accurately detect changes in their disease. And if it gets that far, there will doubtless be cost implications for rolling it out on a grand scale to cancer patients across the UK.

Although these are big questions, we still welcome this important and exciting step, and we look forward to seeing the results of further research in the not-too-distant future.

Kat

Reference:

Forshew, T. et al (2012). Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA Science Translational Medicine, 4 (136), 136-136 DOI: 10.1126/scitranslmed.3003726

Cassandra Jardine (image courtesy of The Telegraph)

We were all very sad to learn that Daily Telegraph journalist Cassandra Jardine died this week after losing her valiant battle with lung cancer at the age of 57.

Cassandra helped to select Cancer Research UK as one of the charities to benefit from the Telegraph Christmas Appeal in 2010 and she wrote a number of heartfelt features in the paper that reflected our work as well as her own experience of lung cancer treatment.

As a result Telegraph readers raised almost a quarter of a million pounds for Cancer Research UK.

Cassandra continued to write about her disease with resilience and humour but without a shred of self-pity. Last year she was the deserving winner of both the Cancer Journalism Award and the Excellence in Oncology Award for her work.

Two weeks before her death she wrote about how she ignored a persistent dry cough – an early symptom of lung cancer. “Aged 55, I was too young and fit for lung cancer to cross my mind. Why would it strike a woman who had never smoked more than three cigarettes a day and had given up some years before?”

At a time when many of us might prefer to suffer in silence, Cassandra continued to work as well as looking after her husband and their five children. She blithely documented the ups and downs of her treatment, the chemotherapy, losing her hair and, in her final months, noted that the drain in her lung was a nuisance that spoiled her dress.

In a tribute her friend and colleague Rupert Christiansen, wrote: “Illness wasn’t something she could take lying down. I marvelled at her clear-eyed attitude to the prognosis and her compassion for those in an even worse condition than she was. Even two weeks ago, when her treatments had been stopped and she knew the end was close, she remained ebullient and optimistic.”

A little over a year ago she wrote this:

“I’m one of the lucky few. More than two thirds of those diagnosed with lung cancer die within a year; one of the two fifty-something women I know who were diagnosed at the same time as me is dead, the other is very sick. But the chemo worked for me. That doesn’t mean the cancer has gone away – it will grow back – but since January I have been able to work, cook, hit (tennis) balls (sometimes) and take the puppy for a walk. No longer do I have to operate my life by remote control, with loyal friends shopping, cooking and making my bed.

“As Easter approaches I marvel at the delicious sense of resurrection. I had forgotten what it is like to feel energetic. I no longer flinch when I see my ghostly appearance topped by wispy hair in the mirror. This return to normal began about two months after the final dose of poison in December when my face, which had been puffy, began to regain its normal shape. Most exciting of all, a fluff of new hair began to cover the shiny bits of scalp.

“For months I had longed for normal, and now I have it – sort of – I am not disappointed. Everything that used to be routine has a thrilling freshness. No one could appreciate the colour of a tulip, the warmth of the sun or even a trip in a rush-hour Tube more than someone who thought they might not experience those things again. Daily, I exchange emails with a reader in Derbyshire who, in a similar position, rhapsodises over the clouds and her children’s vagaries. Maybe everyone needs a dose of illness to appreciate the ordinary.”

Our thoughts are with Cassandra’s family and friends at this difficult time.

Further information

• Watch our video to find out more about the signs and symptoms of lung cancer
• Information for people affected by lung cancer
• Our Cancer Information nurses are available to talk to anyone who is concerned about cancer on freephone 0808 800 4040 (9am-5pm, Monday to Friday) or by email

Not enough evidence to say for sure that working night shifts increases breast cancer risk

A Danish study into whether working night shifts could affect a woman’s risk of breast cancer is hitting the headlines today.

But (as is often the case), when you look beyond the headlines, the picture can become a little less clear.

So could working night shifts cause breast cancer?   The science says “probably”. But probably can be a bit of a tricky word: it isn’t no, but it isn’t really yes either.

So what’s going on? We’ve covered this issue before on this blog, so what does today’s study add to the picture?

The story so far

In 2007 the International Agency for Research on Cancer (IARC), which is part of the World Health Organisation, classified shift working that involves disrupting people’s daily ‘body clock’ cycles as a probable cause of cancer in humans.

That means they looked at all the available research in animals and humans, and summarised it all to decide that although there was enough evidence to show that light during night-time hours could cause cancer in animals, the evidence in humans was limited.

In other words, although many of the studies did show a link, the evidence wasn’t quite strong enough to say for sure that working night shifts could cause cancer in humans.

(For more thoughts on IARC’s classification system, read this post on mobile phones from 2011)

Shifting definitions

One reason for this uncertainty is that studies of the effect of night shifts on women’s health have used different definitions of what a night shift is. This has made it difficult to compare results of different studies.

On top of this, there are also differences in how these studies take account of other factors that are known to affect a woman’s risk of breast cancer, for example her weight, history of pregnancy and childbirth, or how much alcohol she drinks.

None of the studies is perfect, and they have all answered slightly different questions in slightly different ways. And this new study is no exception.

Not the final chapter

Today’s new study has some good points, such as looking at night shift work during all of a woman’s employment history.

And many of the previous studies looked at either nurses or flight attendants, so it had been difficult to say whether the observations were relevant to women in other types of job. This also left open the possibility that any link could be related to the actual job the women were doing, rather than the fact they were doing it at night.

But the new study has three key weaknesses.

Firstly, the number of women with breast cancer in the Danish study was small (only 132) – and only a third of them had actually done shift work before – which limits how reliably we can view the study results.

On top of this, the women were asked to think back over decades of their lives to gather information about their working patterns and other factors, which can make the results biased.

Thirdly, and most importantly, the statistical analysis in the report shows that the researchers can’t be totally confident that their findings aren’t just down to chance: most of the results they found weren’t ‘statistically significant’. This even includes the headline reported ‘40 per cent increase’ in risk.

Only when the researchers looked at the total number of hours of night shifts women worked over the course of their lives, but not the number of years they’d done these shifts for, did they find any significant results.

What if shifts do cause cancer?

Scientists are still trying to come to a consensus about whether shift work truly could increase breast cancer risk, and – if there is a link – to work out how big that effect might be, and how much shift work women could safely do. But based on the available scientific evidence, it just isn’t possible to give a reliable answer to those questions yet.

Some studies have tried to estimate how big shift work’s effect on breast cancer would be, if the link were real. A Cancer Research UK-funded study, published in 2011, estimated that around 2,200 cases a year in the UK could be due to shift work, if a link really does exist. To put that into perspective, the same study estimated around 3,000 cases of the disease were down to alcohol and 4,300 cases to being an unhealthy weight.

So where does that leave us?

The Health and Safety Executive has already commissioned a report into how shift work could affect the risk of various diseases, including cancer. It’s due to be published in 2015, and hopefully will find enough evidence to reach a definite conclusion.

But for now, the answer to the question of whether working night shifts could cause breast cancer is still “probably”. And although this study doesn’t provide the definitive answer, it does still add evidence to the pile – which will be needed if we’re going to resolve the question in future.

Sarah

Sarah Williams is a health information officer at Cancer Research UK

Reference

• Hanssen, J et al. Nested case-control study of night shift work and breast cancer risk among women in the Danish military. Occupational and Environmental Medicine (2012) DOI: 10.1136/oemed-2011-100240
• More about shift work and cancer

Catch up on the cancer news

• Sunday was International Clinical Trials Day. To mark the occasion, Gareth Griffiths, Scientific Director of our Wales Cancer Trials Unit, wrote us an article about the world-class clinical trials being carried out there. Nearly one in five cancer patients in the UK now take part in clinical trials – the highest proportion in the world – and their involvement is shaping the new treatments of the future.
• Flexible sigmoidoscopy – a bowel cancer screening test we helped develop, and which is soon to be introduced in England – reduces the number of new cases and deaths from the disease, a US study confirmed on Tuesday (here’s our news story). But it will be a few years before the test is widely available. We need the Department of Health in England to ensure this technique is rolled out quickly and effectively, and that each of the devolved nations to pledge to use ‘flexi-scope’ in their screening programmes.

• Improving cancer symptom awareness among men with mental illness, and their doctors and carers, could result in improved mortality rates, according to a new study published on Wednesday (press release). The study also showed that those with psychiatric illness are likely to be older when they are diagnosed with cancer – possibly indicating a delay in diagnosis.

• Also on Wednesday, US scientists published research showing that an abandoned sleep disorder drug can target a cancer protein in mice that was previously considered ‘undruggable’ (here’s our news story). More work is needed to see if this lab research can be translated into the clinic, but the idea that medicines that don’t have a current clinical use could be developed to treat cancer is interesting.

• And on Friday, other US researchers showed that an anti-psychotic drug called thioridazine can transform so called ‘cancer stem cells’ into non-cancerous cells that no longer divide (news story here). This is early stage lab work, so it’s too early to say whether thioridazine could be used to treat cancer patients. More broadly though, this work represents just one of several strategies researchers are using to try to kill off cancer stem cells, which are thought to fuel the growth of many tumours.

• We promised in the last news digest that we’d share some news about interesting advances in breast cancer genetics. Henry kept that promise, and in this blog post talks to some of our experts about some fascinating research from the Wellcome Trust Sanger Institute, who’ve used facial recognition software to look for ‘thunderstorms’ in cancer’s DNA.

• We also spotted this story about similar exciting research into prostate cancer genetics. US researchers used powerful next-generation DNA sequencing machines to uncover a distinct subtype of the disease, one that could account for up to 15 percent of all cases. We expect to see many more of these types of these in-depth genetic studies of cancer over the coming months and years.

• Yesterday, we recounted the fascinating – and shocking – story of the tobacco industry’s knowledge and inaction around deadly radioactive polonium in cigarette smoke.

• And, sticking with smoking, new data from the NHS Information Service showed how one in eight pregnant women in the UK still smoke, and how this stat varies around the country. (Here’s the BBC story.) This underlines how much work we still have to do on smoking rates, despite how far we’ve come. The next big priority is plain tobacco packets – sign our petition to help make this a reality.
• The risks and benefits of HRT were again the topic of several media stories this week. Women wanting to know more about the issue this can find detailed information about the current scientific evidence on our CancerHelp UK website.

And finally…

• There were several headlines about coffee drinkers living longer – for instance, this one in the Huffington Post. We thought this would be a good opportunity to discuss the latest evidence about coffee and cancer. The summary: while it might be a great pick-me-up, coffee doesn’t seem to protect against cancer.

• This NHS Choices article about media headlines on snoring and cancer is well worth reading. The long and short of it is that the research on ‘sleep disordered breathing’ and cancer death is certainly interesting, but not without some major limitations. Much more research is needed before any firm conclusions can be made about the affects of snoring on cancer risk – so, any snorers out there: don’t worry.

That’s all for this week – the ASCO cancer conference in the US is looming into view, which is often a busy time for cancer news. More soon!

Olly

Cigarettes contain radioactive polonium

It’s a plot worthy of Hollywood – a fatal radioactive poison, secret documents, suppressed information, and drugs.

But this isn’t fiction. This is the story of the tobacco industry’s knowledge, policy and inaction around radioactive material in cigarette smoke. And how it took a painstaking search through thousands of court-ordered documents to uncover exactly why tobacco firms are unwilling to remove this deadly radioactivity, despite knowing how for more than 30 years.

By their own admission, “creating doubt about the health charge without actually denying it” is a strategy the tobacco industry has used effectively for decades, using smoke and mirrors to deflect mounting evidence of the deadly harm caused by their products.

As politicians and the public debate the merits of putting cigarettes in plain packaging to deter new young smokers, this particular story should serve as a timely reminder of how Big Tobacco operates when faced with the possibility of falling profits.

Setting the scene: radioactivity and cancer

But before delving into the main plot of this real life drama, it’s worth taking a step back to understand some of the basics about radioactivity and cancer.

For many, the word ‘radioactive’ is likely to conjure up emotive images of nuclear power plant catastrophes and mushroom clouds. But it’s not all the stuff of disaster movies. Low-level background radiation is constantly present in the natural environment, both from cosmic rays from outer space and from radioactive material found throughout nature – in the soil we tread on, the water we drink, and the air we breathe.

Low levels of radiation are safe. Even some of the essential elements that make up our own bodies – such as potassium and carbon – have radioactive versions, which add to our background radiation dose.

But higher, concentrated doses of radiation can be dangerous. And long-term exposure to above-normal levels of radiation can be deadly. It’s no coincidence that Marie Curie – who coined the phrase ‘radioactivity’ – died from aplastic anaemia, a disease of the bone marrow that’s now known to be linked to radiation poisoning. She did much of her work in a shed with absolutely no safety measures, and she even carried radioactive material around in her pockets.

One of the earliest links between radioactivity and cancer was made in a small US town called Orange in the 1920s. Women working in a watch factory in the New Jersey town painted the dials with glow-in-the-dark radioactive paint. They frequently licked the tips of the brushes, and inadvertently took in the radioactive element in the paint – radium. Many of these women later developed cancer of the jawbone or mouth, and the use of the deadly radioactive paint was stopped.

Puffing on polonium

Tobacco plants absorb radioactive material

Step forward 40 years from the time of these ‘radium girls’ to the swinging sixties – a time when more than 50 per cent of men and 40 per cent of women in the UK smoked and tobacco advertising was still seen on TV.

In 1964, two scientists from the Harvard School of Public Health published a landmark study that revealed that a radioactive element called polonium in cigarettes could be “significant” in the development of lung cancer.

But how does this radioactive chemical get into tobacco in the first place?

There are two main routes. Some tobacco plants are grown using fertilisers that contain apatite, a group of minerals that becomes contaminated with radioactive lead phosphate, the ‘parent’ of polonium. The plants absorb this radioactivity from the fertiliser.

Tobacco plants also absorb tiny dust particles from the air that are loaded with small amounts of radioactive material, including polonium and other radioactive elements that eventually decay into it. These radioactive dust particles clump onto the sticky, hair-like projections (called trichomes) that thickly cover both sides of tobacco leaves.

Cigarettes deliver dangerously concentrated doses of radioactivity directly into the lungs. When smokers inhale, the radioactive particles damage lung tissue, creating ‘hot spots’ of damage.

Other chemicals in cigarette smoke damage the lung’s cleaning systems, which would normally get rid of gunk in our airways. So the particles build up over time. These localised build-ups lead to far greater and longer exposures to radiation than people would usually get from natural sources.

Autopsies of smokers have shown that cancer often develops where these polonium-induced hot spots of damage occur.

The evidence for the cancer-causing effects of radioactive polonium in tobacco smoke is strong. But instead of addressing these findings in public, the tobacco industry turned to denial and cover-ups.

A deadly cover-up

Take another step forward to the 1990s, when over half a century’s worth of internal tobacco company documents began to be posted online after a 1998 US court order.

Academics have spent years trawling through these 13 million documents to learn about the industry’s scientific research and policy around tobacco. A few years ago we we wrote about a report showing the tobacco industry knew about the danger of polonium in cigarette smoke for over 40 years, but suppressed publication of their research to avoid heightening the public’s awareness of the issue.

This and other studies also found that the industry adamantly resisted efforts to remove polonium from tobacco leaves, and repressed publications about radioactivity in tobacco smoke. Polonium might be only one of many cancer-causing substances in tobacco, but why on earth would the tobacco industry resist the chance to remove one of the deadly poisons in their product?

Professor Hrayr Karagueuzian and colleagues at the University of California wanted to find out, and their recent study seems to have the answer.

The plot thickens

Hrayr Karaguezian studied previously secret documents

Professor Karagueuzian’s team looked in detail at previously unanalysed documents to find out why an industry that makes more than Coca Cola, McDonald’s and Microsoft combined - around £3,500 for every person killed by smoking – is reticent to make its product less deadly.

They were surprised by what they found.

First, the industry was aware of the presence of higher than background levels of radioactivity in tobacco five years before the wider scientific community had published any research on the topic. In 1959, a Canadian health official – by a quirk of fate called Mr Ash – wrote to tobacco company Philip Morris to ask whether tobacco should be regulated as a “radioactive substance”, and suggested a way to remove up to a third of the radioactive dose from cigarettes.

But this letter was “summarily dismissed” by the tobacco company, according to Professor Karagueuzian.

Second, in the 1960s the industry went on to build an in-depth knowledge about the effects of polonium on smokers. They not only knew of potential “cancerous growth” in the lungs of regular smokers, but even accurately calculated how much radiation a long-term smoker would take in.

And despite knowing how to remove the deadly radioactivity for several decades, the industry was “unshakable and adamant with respect to its policy of silence, denial, obfuscation, and rebuttal to any and all from of news about tobacco radioactivity”.

The reason? Professor Karagueuzian is convinced profit underpinned this silence and denial.

The final twist: nicotine free-basing

Over 30 years ago, scientists discovered that a process called “acid washing” removes almost all of the polonium from tobacco. But the tobacco industry refused to use it to remove the radioactive material from their products.

Officially, they said the process would cost too much and might have a negative impact on tobacco farmers and on the environment. Karagueuzian says accepting this logic is “tantamount to accepting that inhalation of radionuclides by smokers is the safest way to dispose of excess tobacco radiation”.

The newly studied documents reveal a potentially more plausible reason why the industry avoided acid washing – the process alters the nicotine in tobacco leaves and makes it less able to deliver the instant nicotine rush smokers craved.

The chemical ammonia is added during the processing of tobacco leaves, which ensures most of the nicotine in cigarettes is in a ‘free base’ form that is more quickly and easily delivered to the brain. Crucially, the acid wash process counteracts this ‘free-basing’ effect. It adds a positive charge to nicotine molecules, which are then delivered more slowly to the brain, depriving smokers of the full effect of the drug.

The term free-basing has more commonly been associated with cocaine addiction, where users seeking a more intense effect from the drug convert it from its normal form to its more intense free-base form.

Free-basing is about giving addicts a drug ‘kick’ as quickly and efficiently as possible. It’s not hard to imagine why an industry that relies on addicts being hooked on their deadly products would resist a process that reduces the effect of their key drug.

Smoking kills – so we need to stop people starting

Let’s be crystal clear: polonium polonium isn’t the only killer in tobacco. There are more than 70 cancer-causing chemicals – including arsenic and formaldehyde – and hundreds of other poisons in a single cigarette.

Tobacco will kill one billion people in the 21st century if trends continue, one sixth of the current world population. That’s one person dying every six seconds. And those incomprehensible numbers don’t speak of the countless family members and friends who have to cope watching their loved one die, and then carry on with life after they have gone.

Despite some legislative successes in the UK aimed at reducing the number of smokers, tobacco is clearly still a colossal health problem.

Give children one less reason to start smoking

The best protection from tobacco is not to smoke it in the first place. And if we’re to beat cancer, then stopping as many new smokers entering the market as possible is clearly a route we must follow, and campaigning for plain packaging of cigarettes could help. Although it won’t stop current smokers, it will help give millions of kids one less reason to start. Quite simply, it will help to save lives.

But it will also damage tobacco industry profits. The story of polonium highlights the twists and turns made by an industry that puts profits above health, and continues to push a product that kills half of all its long-term users.

Make a stand

This story should serve as a stark reminder to those who hear the tobacco industry’s counter arguments about the effects of plain packaging of their product.

Perhaps the following quote will help to explain not just why removing radioactivity has been refused by the tobacco industry, but also more broadly why they resist efforts to make their product less appealing:

“Tobacco products, uniquely, contain and deliver nicotine, a potent drug with a variety of physiological effects… if we meekly accept allegations of our critics and move toward reduction or elimination of nicotine from our products, then we shall eventually liquidate our business. If we intend to remain in business and our business is the manufacturer and sale of dosage forms of nicotine, then at some point we must make a stand.” - Claude E Teague Jr, Assistant Director of Research at R.J. Reynolds Tobacco Company, 1972

Our business is beating cancer. So we must make the strongest stand possible against the industry that is responsible for millions of deaths from this disease.

If you want to join us, please sign our petition.

Reference

Karagueuzian, H., White, C., Sayre, J., & Norman, A. (2011). Cigarette Smoke Radioactivity and Lung Cancer Risk Nicotine & Tobacco Research, 14 (1), 79-90 DOI: 10.1093/ntr/ntr145

The Wellcome Trust Sanger Institute in Cambridge

Nestling in the Cambridgeshire countryside, the Wellcome Trust Sanger Institute is a hot-bed of cutting-edge genetic research.

The Institute played a key role in deciphering the human genome at the turn of the millennium, and is continuing to make huge strides in mapping humanity’s evolutionary history, and the diseases that affect us.

As you might expect, a substantial portion of the Institute’s work focuses on cancer. Its director, Professor Mike Stratton, has a long history in this field, having helped lead the efforts to hunt down genes like BRCA2 and BRAF (work we’re proud to have supported).

And thanks to places like the Sanger, and other labs and institutes around the world, it’s an incredibly exciting time in cancer genetics research.

Just last month, we wrote about a landmark Cancer Research UK-funded study called METABRIC, led by researchers at our Cambridge Research Institute. METABRIC redefined breast cancer as ten separate diseases, based on how genetic mutations driving each tumour were related to how long women survived their disease.

This week, the Sanger’s researchers have built on this work, releasing three tour de force research papers, providing even more detail of what’s turning out to be a extraordinarily complex disease.

Nine new breast cancer genes

As we reported on our news feed, the first paper (published in Nature) described the discovery of nine new genes involved in breast cancer. It also confirmed one of METABRIC’s key findings – that breast tumours are phenomenally genetically diverse, but important similarities exist between them.

While METABRIC focused mainly on large scale flaws in DNA – so-called ‘copy-number variations’ (where whole stretches of DNA are repeated or missing) this study looked in more detail, looking for tiny faults in the entire complement of active genes – known as a tumour’s ‘exome’ – as well as copy number changes, across 100 different breast cancer samples.

Every cancer they analysed was different, and no two women’s tumours were 100 per cent identical. But as well as this diversity (“a sobering perspective”, in the words of Professor Stratton) there was also some good news.

Many of the faulty genes were found to belong to the same molecular pathway or process. For example, several genes belonged to a signalling network called ‘JUN signalling’. Others regulated the winding and unwinding of DNA – a process called chromatin remodelling.

Focusing on such similarities, rather than the daunting diversity, will help further refine how researchers and doctors classify and treat breast cancers in future.

Molecular mechanisms and family trees

But how do all these DNA faults arise, and in what order? The Sanger Institute’s researchers have begun to sketch out some tentative answers in two more papers, both published in the journal Cell.

These studies focused on a repeated DNA analysis of a single tumour from a woman with oestrogen receptor-positive breast cancer – the most common form of the disease.

The Sanger team mapped out DNA errors in samples of this tumour again and again, 188 times in all, cataloguing individual mutations present in each sample.

In the first analysis, they then sifted through the resulting data mountain using powerful computer programmes, originally developed as facial recognition software.

This allowed them to compare the context of each error in the DNA code – in other words, to look at the ‘letters’ either side of each ‘spelling mistake’ – to see if patterns emerged.

And they did. The researchers identified five clear signatures, each corresponding to a different biological process at work as the tumour developed. And they then looked for – and found – the same signatures at work in a further twenty tumours.

They also spotted an entirely new and perplexing phenomenon, which they termed ‘kataegis’ (after the Greek for ‘thunderstorm’), where specific regions of the tumour’s DNA had mutated extraordinarily rapidly at a particular time in its history.

But what was causing these signatures?

Detailing the damage

The researchers discovered 'thunderstorms' in the genome

The researchers compared what they’d seen to what’s currently known about DNA error and repair pathways, to see if they could work out what was going on.

But they could only definitively link one of the five observed signatures to a process known to be involved in cancer – the conversion of a modified version of a DNA ‘letter’ called cytosine (a ‘C’ in the DNA code) to thymine (a ‘T’), when the ‘C’ comes before a ‘G’ – a guanine.

They have their suspicions about what might be behind the other four (and excitingly, one of the prime suspects is a process we’ve blogged about before), but this is the starting point for a very exciting period of research. Knowing the precise molecular forces at work as a cancer develops is exactly the sort of intelligence that could transform our ability to fight cancer.

But the researchers didn’t stop there. Their second analysis tried to find out when particular mutations arose in a cancer’s history.

It’s all in the timing

If tumours contain genetically different populations of cells, that evolved from a common ancestor, then each sample from a tumour should give a slightly different set of results when it’s DNA is analysed.

So measuring how often different genes are mutated in different samples, mapping these gene mutations to different regions of chromosomes, and applying some pretty sophisticated maths to the results, should allow a tumour’s genetic past to be reconstructed.

And so, again, the researchers started off with data from the single tumour they’d analysed 188 times, but now they looked at how often each mutation or DNA rearrangements occurred in each of the 188 analyses.

And again, the researchers turned to sophisticated computer algorithms – this time to look for patterns to help them reconstruct the tumour’s ‘family tree’. And just as before, they repeated their analysis in twenty other tumours, testing and confirming their findings.

As anticipated, each tumour seemed to be made up of different populations (‘subclones’) of cells, each stemming from a common ancestor unique to each patient, and yet each subtly different. They also found that each tumour had a dominant population of cells, making up at least half of the tumour. And they were able to get a sense of the time-span over which these populations evolved.

Putting all this together, the researchers deduced that a tumour can exist for some time as a tiny colony of subtly different mutated, growing cells, until one colony, for reasons unknown, suddenly takes over, growing rapidly and – ultimately – causing symptoms.

But a second crucial finding, one that gives hope to cancer researchers everywhere, is that mutations in so-called ‘driver’ genes tended to occur early in a tumour’s lifetime – in the ‘trunk’ of the tumour’s family tree. This suggests that treatments aimed at these gene faults will continue to show promise.

What happens next?

More work is now needed to understand exactly how tumours originate, grow, evolve and diversify.

Professor Carlos Caldas, who led the METABRIC study with colleagues in Canada and contributed to last week’s Nature paper, said the new data would be vital to future genetic cataloguing of breast cancer.

“This will feed into other researchers’ work, including that of my own group”, he told us. In Caldas’s view, cataloguing and exploring these mutations in larger numbers of tumours will be essential.

As he points out, the researchers analysed a lot of DNA, but it only came from a relatively small number of patients – these findings need to be scaled up to thousands or even tens of thousands of samples. Although this research is groundbreaking stuff, our knowledge of how all this fits together is still, Caldas says, “preliminary”.

“We’re still only seeing part of the picture. We need to be looking at how cancer continues to evolve after its spread,” he argued, which means analysing samples of secondary tumours from patients with advanced disease.

And he also pointed out that current DNA sequencing technology isn’t perfect, and this meant some types of tumour couldn’t be analysed – particularly smaller tumours, or tumours with a high proportion of non-cancer cells. “We’ve not even begun to look at the whole spectrum of breast cancers – just the ones we can analyse using the tools we have available,” he said.

Nevertheless, he said, this is “an extremely important piece of work, and it’s exciting that so many recent discoveries are converging around the same ideas,” of diversity and underlying similarity.

Professor Charles Swanton, the London-based Cancer Research UK scientist whose work on evolutionary diversity in kidney cancer caused such excitement earlier this year, agrees that the work “provides crucial insight” into the range of genetic diversity in individual tumours.

“Importantly, these papers begin to shed light on the way in which this diversity appears – a key step towards working out how to stop it arising in the first place,” he told us. Ultimately, Swanton hopes, we’ll use this knowledge to improve outcomes for patients with breast cancer and other cancers. After all, the principles at work here are likely to be common to more than just one form of the disease.

So what do all these genetic studies say about our progress against this terrible disease?

We know that cancer is incredibly complex, yet driven by common principles.

We also know that tumours are diverse, ever-changing collections of genetically damaged cells, but that by aiming our expertise and technical knowhow at them, we can begin to understand, unpick – and hopefully conquer – the processes that cause them.

And we know that a new era of genomics research is finally allowing us to read cancer’s inner secrets, deciphering their life history in ever greater detail.

As the Sanger team said in their Cell paper, “The cancer genome is like a palimpsest, an ancient parchment that was frequently reused, each time retaining traces of what had previously been written”.

It’s a parchment we urgently need to translate, so that we can convert this breathtaking explosion of new scientific knowledge into treatments to help the cancer patients of the future.

Henry

References

• Stephens, P. et al (2012). The landscape of cancer genes and mutational processes in breast cancer Nature DOI: 10.1038/nature11017
• Nik-Zainal, S. et al (2012). Mutational Processes Molding the Genomes of 21 Breast Cancers Cell DOI: 10.1016/j.cell.2012.04.024
• Nik-Zainal, S. et al (2012). The Life History of 21 Breast Cancers Cell DOI: 10.1016/j.cell.2012.04.023

Coffee: a nice pick-me-up, but not a cancer buster

Coffee is a big part of many people’s lives, but it’s not thought to have many health benefits – it keeps you awake, and often has lots of sugar, milk or cream added, which can pile on the calories.

But lots of studies have looked into whether coffee could have greater effects on the body other than waking you up – including whether it could affect your chances of developing cancer.

The results of these studies have been conflicting – especially those that have looked at different types of cancer, with some indicating coffee could be beneficial, others that it could be harmful, and yet more showing that it has no effect on cancer risk or the risk of dying from cancer.

Among all this conflicting evidence, a new study has been published in the New England Journal of Medicine, following more than 400,000 people for up to 13 years, to search for links between the amount of coffee they drank and their likelihood of dying from any cause during the course of the study, including cancer.

The results showed that drinking coffee could reduce ‘all-cause mortality’ – the chance of dying from anything – and the risk of dying from certain other conditions, but it had no effect on the risk of dying from cancer.

What did they find?

The researchers looked into the risk of dying from several different diseases – cancer, heart disease, diabetes, lung disease, infections, stroke – and even accidents. Many of these causes of death were less likely among heavier coffee-drinkers, but not cancer. In fact, cancer death rates stayed pretty much the same, no matter how much coffee people drank.

There’s also an interesting observation buried in the statistics.

Although overall death rates were lower in coffee-drinkers, this was only apparent after the results had been adjusted to take into account all the other things that might affect the risk of dying.

In particular, smoking had such a strong effect that without adjusting the results to take it into account, the overall risk of dying initially seemed to be higher among coffee-drinkers, because people who drank the most coffee were also more likely to be smokers.

It might sound like an obscure statistical point, but it does serve as a useful reminder that coffee, like so many other aspects of our diet and lifestyle, isn’t a ‘magic bullet’ or a guarantee against disease. And small positive effects from one thing can easily be outweighed by other aspects of our lifestyles.

And here’s another important point – because this study just looks at the likelihood of dying for different levels of coffee-drinking, it can’t show anything about whether it’s the coffee itself causing the reduced risk of dying, or some other reason that’s linking the two things. In other words, it doesn’t show cause and effect, just a statistical link.

What does all this mean?

In essence, while drinking coffee tastes great, may help keep us awake, and might protect against other diseases, it doesn’t seem to protect us against cancer.

There are plenty of things you can do that are reliably known to reduce cancer risk – being a non-smoker, keeping a healthy weight and drinking less alcohol, to name but a few.

But as for coffee, it won’t be making it onto that list for now.

Jess

Reference

• Freedman, N. et al. (2012). Association of coffee drinking with total and cause-specific mortality New England Journal of Medicine, 366 (20), 1891-1904 DOI: 10.1056/NEJMoa1112010

James Lind (1715-1794) - the father of modern clinical trials. Image from Wikimedia Commons

May 20^th was International Clinical Trials Day, first established in 2005 to raise awareness of the importance of clinical trials.

To recognise this, Gareth Griffiths, Scientific Director of the Cancer Research UK Wales Cancer Trials Unit – one of our seven pioneering trial units around the UK –  tells us about the international importance of his Unit in running world-class clinical trials.

But first, a bit of history…

The first clinical trial

20^th May was chosen to mark the first recorded controlled clinical trial back in 1747, when a Scottish naval surgeon called James Lind carried out a clinical trial on sailors with scurvy. He gave a number of sailors either cider, vinegar, seawater or oranges and lemons in addition to their normal rations.

Lind found that the sailors who received 2 oranges and a lemon every day recovered from scurvy, providing the first hard evidence that citrus fruits in the diet prevent scurvy. James Lind published his findings and as a consequence the British Navy began to supply their ships with limes to prevent scurvy – hence the old nickname “limeys”.

Although the techniques may have moved on since Lind’s time, clinical trials remain the gold standard of scientific evidence for the effectiveness of treatments for diseases such as cancer.

Clinical trials in cancer

Most cancer trials fall into one of three ‘phases’, depending on their size and aims. This diagram explains the difference:

Introducing the Wales Cancer Trials Unit

The Wales Cancer Trials Unit, based within the Cardiff Cancer Research UK Cancer Centre, is an All-Wales clinical trials unit carrying out studies of new cancer drugs and different ways of giving chemotherapy, surgery and radiotherapy. The Trials Unit recruits cancer patients from hospitals across Wales via the Wales Cancer Research Network nurses, funded by the Welsh Government and Cancer Research UK.

Furthermore, the Unit not only carries out clinical trials in Wales and the rest of the UK but also internationally, and the results from the trials provide evidence to justify new, better treatments for the cancer patients of Wales and beyond.

Here are just a few examples of the pioneering clinical research going on at the Unit:

International clinical trials in leukemia

The Unit is running an important Cancer Research UK-funded clinical trial in leukemia called AML17, led by Professor Alan Burnett at Cardiff University. This large-scale trial is looking at a number of new drugs to treat acute myeloid leukemia in younger people and needs to recruit thousands of patients.

The trial started recruiting in Wales and the rest of the UK but has recently opened to patient recruitment in Denmark and New Zealand. When the results come out in about two years’ time they could change the way this disease is treated around the world.

International trials in Welsh Hospitals

The Wales Cancer Trials Unit worked with Professor John Wagstaff at Swansea University to open a trans-European kidney cancer clinical trial in the UK called SURTIME. This is a study looking at when to give surgery, either before giving the cancer drug sunitinib (Sutent) or later on after drug treatment has started, to see which timing is most effective at treating the disease.

Led from Brussels, the trial was originally only open to patients in mainland Europe. But Cancer Research UK funded the Wales Cancer Trials Unit to open SURTIME to cancer patients in Wales and the rest of the UK. This has resulted in a truly international collaborative trial which will help to find the best treatment for kidney cancer patients.

Building international collaborations

Some cancers are rare (for example, salivary gland cancer) and there aren’t enough patients in any one country to run trials big enough to properly investigate new treatments.

Cancer Research UK has spearheaded an initiative with the US’s National Cancer Institute and the European Organisation for Research and Treatment for Cancer (EORTC) to investigate how the UK, US and other European countries can work together to recruit enough patients for trials in rare cancers.

As a result of this International Rare Cancers Initiative, more trials in rare cancers should become available to Welsh and UK cancer patients in the future. And because of my involvement in this initiative, I’ve been invited onto the United States National Cancer Institute International Planning Committee representing Cancer Research UK. This group is looking to create a network of countries across the world, including countries in Europe, North America, South America, China and Japan, kick-starting an exciting new era of international clinical trial collaboration.

The most important people are the patients

Although clinical trials units like the one in Wales are an essential part of the process, life-saving cancer trials simply wouldn’t be possible without the patients who volunteer to take part.

Nearly one in five cancer patients in the UK now take part in clinical trials – more than anywhere else in the world – and their involvement is shaping the new treatments of the future. By contributing to this vital work they are helping us make huge progress towards beating cancer, and we owe them a huge debt of thanks.

Gareth Griffiths, Cancer Research UK Wales Cancer Trials Unit

• To find out more about cancer clinical trials running in Wales and throughout the rest of the UK, have a look at the clinical trials database on the CancerHelp UK website.