Clinical trials, breast cancer clues and immunotherapy progress

Cancer Research UK
This month - funding boosted for UK cancer trials, 100 days until tobacco displays are removed, scientists uncover breast cancer clues, processed meat increases pancreatic cancer risk, we look at the latest progress in immunotherapy, and finally, there’s a glimpse of what 2012 holds for Cancer Research UK.



Welcome to the Cancer Research UK podcast. I’m Aaron Eccles.

The network of Experimental Cancer Medicine Centres, or ECMCs, has been given a £35 million funding boost over for the next five years. The money comes from Cancer Research UK and the Departments of Health for England, Scotland, Wales and Northern Ireland.

First set up five years ago, the network has grown to 18 centres around the UK, running early stage clinical trials of brand new cancer treatments.

Although the patients taking part in these trials are usually very poorly and may not have long to live, the ECMCs provide access to the very latest treatments and the results of the studies could help to save other people in the future.

So far, the ECMC network has supported more than 2,000 studies across 25 different cancer types, involving many thousands of cancer patients.

Dr Joanna Reynolds, Cancer Research UK’s director of centres, told us about the impact the network has had so far.

“The ECMC funding has underpinned the development of some of the most promising and innovative new cancer drugs which are already on the path to becoming established treatments for future cancer patients. One example is that the ECMCs played an important role in the early phase trials of abiraterone, which was approved for use in advanced prostate cancer last year.

Also last year the ECMCs were reviewed by an international panel of experts and they said that the network is an outstanding asset to the UK and a platform on which to build.”

The countdown has begun for supermarkets to begin removing tobacco displays from their shops with just 100 days left for retailers to comply with the new law.

The ban, which will come into force on 6th April, is intended to protect young people who are often the target of tobacco promotion.

Cancer Research UK supporters were instrumental in bringing about the ban after years of campaigning through our Out of Sight Out of Mind campaign.

We spoke to Robin Hewings, Cancer Research UK’s director of tobacco control, to find out why banning tobacco displays is so important in the fight against cancer.

“We think this is a really good policy and we’re really pleased that it’s going to be brought into effect over the next few years in different parts of the UK. The reason for that is because over a quarter of deaths from cancer are due to smoking, so it’s something that’s really important as an organisation for us to tackle.

One of the best ways of doing that is to stop people from starting [smoking]. People tend to start as teenagers, so we need to stop teenagers from taking up smoking. The reason why tobacco displays are important is that we have tobacco on open display in shops next to everyday products like razor blades, sweets or crisps.

That sends the message that smoking is a normal everyday activity, when what’s really important is to show people that this is a deadly, addictive drug. So it’s right that they’re not on open display in shops”

Scientists from Cancer Research UK’s Cambridge Research Institute have taken a step forward in understanding why some breast cancers become resistant to treatment, or come back after therapy.

Many breast cancers are fuelled by the female sex hormone oestrogen, which attaches to particular regions of DNA within cells and turns on important genes. The Cambridge team discovered that receptors for the oestrogen were attaching to different DNA regions in cells from breast cancers that were more likely to resist treatment compared to cancers that did respond well. This revealed a specific set of genes that are turned on in the resistant cancers.

Crucially, they also found that within these particular tumours, the oestrogen receptor was being ‘redirected’ to different regions of DNA by a protein called FOXA1.

Study leader Dr Jason Carroll explains how this knowledge could one day be used to help women whose cancers have become resistant to treatment.

“What this study showed is that all oestrogen receptor-positive breast cancers – which make up the bulk of breast cancers – are not the same. We’ve know that’s the case, but this study shows us that the protein (oestrogen receptor) does different things in different types of breast cancers. So it can sit on different regions of DNA in the human genome and it can switch on or switch off different genes. And these two different states, ultimately, are linked with the clinical outcome of patients.

We think this is important because it tells us first of all that the oestrogen receptor is still important even in drug-resistant breast cancers, which we weren’t sure was the case. It also gives us insight into why this happens. Now we know that it occurs, we can pull it apart and try and understand how it is that the protein can ‘hop around’ the genome, and we can use that information to try and understand what it is we need to be doing to treat these women.

And that’s exactly what we’ve been doing – we pulled the machinery apart once we’d found it and found there was a protein called FoxA1, which seems to be critical in allowing the oestrogen receptor to move around the genome. This has reaffirmed to us that this is what we should be making drugs against, and that’s exactly what we’re doing.

The first thing we need to do is validate this – this was done on a small-ish cohort of women, so we need to validate it in a much larger collection of women. We are using the information to start a large-scale screen to find chemicals that will specifically block this protein we’ve discovered, called FoxA1, so if we can do that we think we may have a way of treating women who are oestrogen receptor-positive but whose cancers are resistant to classic oestrogen receptor drugs [e.g. tamoxifen]”

Eating too much processed meat increases the risk of pancreatic cancer, according to new research published in the British Journal of Cancer this month.

The study found that for each 50 grams of processed meat eaten every day – equivalent to a sausage
or two rashers of bacon – there was a 19 per cent rise in the risk of pancreatic cancer compared to those who ate no meat.

The researchers also looked for links between unprocessed red meat and pancreatic cancer. However, the evidence here was less conclusive, with an increase in risk seen in men but not women. This may be because men in the study tended to eat more red meat than women.

Yinka Ebo, senior health information officer at Cancer Research UK, tells us what diet advice we should take from this study.

“The jury is still out as to whether red meat is a definite risk factor for pancreatic cancer, so we do need to see more large studies to confirm this. But this analysis does suggest that processed meat may be playing a role.

But the important thing to remember is that there is a relatively low risk of developing pancreatic cancer in the first place, and that processed meat adds a small risk to this. And among the lifestyle factors, smoking significantly hikes up the risk of pancreatic cancer, so stopping smoking is the best way to reduce your risk of the disease, as well as many other cancer and other diseases as well.”

The role of immunology is set to continue to have a big impact in cancer research this year. Last year the Nobel Prize in Physiology or Medicine was jointly awarded to three immunologists whose discovered underpinned research into harnessing the immune system for the treatment of cancer and other diseases.

Our reporter Nell Barrie, spoke to Dr Caetano Reis e Sousa, a leading Cancer Research UK immunology expert at our London Research Institute, to find out about the latest progress in this exciting field.

“Immunology is the study of the immune system, and the immune system is an organ inside our bodies that protects us from disease. It is not an organ in the usual sense of a mass of cells in one place, it’s rather an organ that’s dispersed because it’s made up of white blood cells that effectively travel everywhere looking for invaders. It is now clear that the immune system can protect us not only from infection – which is what it evolved to deal with – but also from cancer.”

Nell: Can you explain a little bit about the recent Nobel Prize that was won for research into immunology? What was this prize looking at, what was the research behind it?

“The prize actually rewarded three people who were working on two different aspects of immunology that have come together in recent years. The background to this is that these white blood cells of the immune system are effectively mobilised in response to infection, and the “generals” of this “army”, as it were, are called T-cells. Now, T-cells need to be told that there is an invader, and it turns out that this is the job for another type of white blood cell called a dendritic cell, that was discovered by Ralph Steinman – one of the Nobel recipients.

But more than presenting foreign intruders to T-cells, the dendritic cell instructs the T-cell to attack those invaders, and it does so because it’s able to recognise the molecular signatures of infectious organisms. The discovery of the receptors that allow the dendritic cell to do this, by Jules Hoffman and Bruce Beutler, was rewarded also by their share of the Nobel Prize this year.”

Nell: Can you explain what progress has been made in immunology since these discoveries we’re talking about?

“There has been a huge explosion of research in immunology triggered by these discoveries. Number one, the primacy of dendritic cells as the sentinels of the immune system that then instruct T-cells to attack has led to a whole new way of thinking about vaccination – both in infectious diseases but also in cancer immunotherapy.

In addition, the understanding that there are specific receptors that, in turn, tell the dendritic  cell that something odd is around has led a number of research groups to focus on the notion that perhaps if we can activate the receptors directly, we can fool the immune system into thinking that something noxious is around that needs to be attacked. And this could be quite useful in terms of inducing potent responses against cancer.”

Nell: This technique is being used now to boost the immune system and try to get it to target cancer cells. Can you explain a little bit about how that’s working at the moment?

“Effectively, cancer cells are ‘foreign’ to the body, and therefore they have the potential to be attacked by the immune system. But because they don’t necessarily have the same signatures as microbes, they don’t generally cause a very potent attack. You can draw an analogy with a baby growing inside a pregnant woman’s body – it is foreign to the body but it does not elicit an immune attack because it doesn’t mimic a bacterium or a virus.

So one of the ways in which we can try and use this new knowledge to design novel immunotherapies for cancer is to deliver to the dendritic cell bits of the cancer, but mask them with these ‘signatures’ of infectious organisms, to effectively fool the dendritic cell into thinking it is not the equivalent of, say, a baby growing inside you, but a nasty infection. In so doing, the dendritic cell will them instruct T-cells to attack.

And this is now being used at a number of different levels. There are strategies which allow you to deliver bits of tumour directly to dendritic cells. Another strategy involves trying to isolate the dendritic cells from patients and then manipulate them in the test tube before putting them back into the patient.

So those two strategies are going hand in hand, and there are multiple variations on these – all of which are still at very early stages of research and just entering clinical trials, so it’s still a long way before we will know if they will, in fact, be useful or not. “

Nell: Tell me a little bit about your research – what are you focusing on at the moment?

“Our research focuses exactly on this area. We have a general interest in dendritic cells and trying to understand the biology of these cells, but we also have a very large investment in trying to decipher and describe the receptors that are used by the dendritic cells to ‘sense’ that a pathogen is around.

We have described ourselves a number of these receptors and what they recognise, and what, in turn, that allows a dendritic cell to do – all of which can be used by Cancer Research UK to then develop further translational approaches that will potentially lead these discoveries to cancer immunotherapy.”

2011 was another busy year for us. Our scientists, doctors and nurses across the UK worked hard to understand cancer, and find more effective ways to prevent, diagnose and treat it.

Some of highlights for the charity have been a new drug for advanced prostate cancer being licensed in the UK, an end to tobacco vending machines, and the launch of our Stratified Medicine Programme - a vital step in making personalised cancer treatments available to cancer patients in the UK.

We spoke to some of our experts to find out what they are working on and their hopes for continued progress in cancer research this year.  

“I’m Peter Johnson, Chief Clinician here at Cancer Research UK.  2011 was the year that we saw our Stratified Medicine Programme launched, which is our ambitious attempt to bring routine molecular testing into cancer diagnosis. We’ve launched a programme to recruit 9,000 patients across seven centres in the UK over the next two years, and show that we can get a lot of information about the molecular makeup of their tumours.

Looking forward into this year, this programme will really take off and expand. And linked to that, I’m looking forward to seeing yet more drugs coming through into the clinic based upon the molecular characteristics of tumours. We’ve seen vemurafenib for melanoma come through last year, we’re going to see crizotinib for lung cancer come through this year, so it’s a very exciting time.

There’s a continuing stream of new agents coming through and I think our Stratified Medicine Programme is going to be leading the way worldwide for how you do this in practice.”

“I’m Nic Tapon, I’m a Cancer Research UK scientist at the London Research Institute in central London, and my lab is interested in trying to understand how the cells that make up our tissues stop growing and dividing so that we don’t get cancer.

Cancer Research UK is taking part in a massive new science project for the UK called the Francis Crick Institute, which is going to be built next to St Pancras train station. The building started in 2011, and in 2012 we’re very excited about the prospect of working more closely with our colleagues at the National Institute for Medical Research and also at University College, Imperial College and King’s College in order to build this amazing new joint venture which is really going to change the face of British science.

The most exciting thing about science right now is how fast things are moving. What I’m looking forward to the most for the coming year are all the amazing new, unexpected findings that 2012 is going to bring for cancer research.”

“I’m Carlos Caldas, I’m a professor of cancer medicine at the University of Cambridge and a senior group leader at the Cambridge Research Institute.  [There were] two major highlights from the work in my laboratory [last year] - one was the discovery of Znf703 as the newest breast cancer oncogene. There have been no new breast cancer oncogenes discovered in the past five years and so it was very nice to finally be able to identify the driver at chromosome 8p12.

The second is that our molecular pathology efforts, in collaboration with Paul Pharoah at the Strangeways Research Laboratory, by characterising tissue microarrays from a very large population-based collection have solidified our view of the different subtypes of breast cancer and how they correlate with prognosis.

2012 starts well with the story of the ER-binding genome-wide – the collaboration between my lab and Jason Caroll’s lab that shows the patterns of binding of ER are variable in oestrogen receptor-positive patients and they are associated with different outcomes. I think that we will follow on from this and we are in the middle of reporting our findings from the largest genomic profiling exercise ever done in breast cancer –nearly 2,000 breast cancers that we have profiled – and we are in the final stages of having that paper hopefully accepted by one of the major biomedical journals.

And the second thing is going to be that we are going to be sequencing more breast cancers and starting to have characterisation at the single nucleotide level of the molecular heterogeneity of breast cancer. This will have a major impact in the way we diagnose breast cancer, in the way we classify breast cancers into subtypes with different prognosis and different responses to therapy, and hopefully also identify novel targets for treatment.”

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