Notes from NCRI conference (day 4)

That’s all folks!

Before the final day of the conference started, we once again awoke to news stories based on research presented over the last few days.

The BBC led with figures released at the conference showing that the economic cost of cancer tops £15bn a year in the UK. Drawing on the same figures, the Daily Mail highlighted the staggering toll of lung cancer in the UK – £2.4 billion per year – which is more than other common cancers such as breast and bowel.

We agree with their headline that there’s an urgent need to stop younger people from taking up smoking – the major cause of lung cancer.

Prostate cancer – doing better than “hoping for the best”

The last day of the 2012 NCRI Cancer Conference opened with a talk from Dr Robert Bristow, a prostate cancer expert from the Princess Margaret Hospital in Toronto.

Bristow described how men with prostate cancer can be divided into three groups – low risk (men with slow-growing tumours that don’t need immediate treatment but should be monitored), high risk (men with aggressive, invasive cancers that need urgent, intensive treatment) and intermediate risk (men whose cancers are growing but not spreading, who are usually  treated with surgery and/or radiotherapy).

Unfortunately, cancer comes back in around one out of every five ‘intermediate’ men. Dr Bristow wants to find out why, and develop better treatment options. He’s shown that men with intermediate cancers whose tumours have more messed-up DNA (known as genomic instability) and lower oxygen levels (hypoxia) are likely to do worse after surgery or radiotherapy.

Working in collaboration with researchers at our Gray Institute in Oxford, he’s found that giving these men drugs called PARP inhibitors before they have radiotherapy can help to improve things.

Turning to the explosion of genetic knowledge about prostate tumour genetics, Dr Bristow then showed how men with intermediate risk prostate cancer can be divided into four “genetic clusters”, with clear differences in how well they respond to treatment. He described a large clinical trial that he and his team are setting up, called MATADORS, selecting men whose cancers have lots of genomic instability and hypoxia and offering them new treatments (including PARP inhibitors and other drugs) rather than standard surgery or radiotherapy. Hopefully, this approach could change the odds for men with intermediate risk prostate cancer.

Finally, Dr Bristow highlighted the importance of the International Cancer Genome Project (ICGC). He’s working together with our scientists at The Institute of Cancer Research in Surrey to analyse the DNA inside of hundreds of prostate tumours. By digging through all this genomic data, prostate cancer researchers all over the world are making real progress in understanding this disease, and how to get the right treatment to the right men at the right time.

An aspirin a day? Not yet

In one of several parallel sessions this morning, we heard about aspirin’s potential role in preventing cancer – a topic that’s been widely covered in the press over the years, and which Jess reviewed here earlier in the year.

Given the now very strong evidence that taking regular aspirin could reduce the risk of some cancers, especially bowel cancer, the session ended with a bit of a debate about whether people should take aspirin, and if so, who would be most likely to benefit.

But it’s not a simple question to answer – aspirin causes a range of serious side effects like internal bleeding, so unfortunately there aren’t any clear answers yet for most of the population.

Professor Sir John Burn may have answers for at least some people, though. His work with people who carry a particular type of genetic mutation putting them at high risk of cancer (Lynch syndrome, or HNPCC) has led him to think that most people in this group should take aspirin for cancer prevention. That’s good news for people with Lynch syndrome, but can we find a general rule for the rest of the population? The jury’s still out. Indeed, some of the speakers in the session already take aspirin themselves, but others don’t.

We hope that research will help us make recommendations at some point soon, but in the meantime, before you reach for the medicine cabinet, talk to your doctor as there are common conditions and medicines that mean aspirin may not be suitable for everyone.

Personalising therapy in blood cancers

Carrying on one of the major themes of this year’s conference, Dr Faith Davies from The Institute of Cancer Research led a session about the clinical implications of  cancer evolution,

particularly as they relate to two cancers that don’t often get the focus of conferences like NCRI – acute myeloid leukaemia (AML) and multiple myeloma.

Cancer Research UK’s Professor Alan Burnett spoke about the “tsunami of molecular information” clinicians are now faced with. He discussed his own research into AML, and how such information about the genetic markers of disease is helping doctors group patients into different risk groups and to choose the best course of treatment for them – for example, deciding which patients will benefit most from stem cell transplants.

Professor John Welsh from Washington University then discussed his group’s work to sequence the entire DNA sequence of the cancers of 24 AML patients. The results of his research chime with many of the other presentations from the meeting this year – that different populations of tumour cells evolve their own set of gene faults over time, like in the branching species evolution tree first described by Charles Darwin.

Crucially though, there may be some key faults in the ‘trunk’ of this tree that we should try to identify and target.

Professor Gareth Morgan wrapped up this interesting session, looking at the genetic evolution of myeloma. He said that although there’s been significant progress in treatment over the past 10 years, more needs to be done to improve survival rates. He thinks that viewing cancer through the prism of Darwinian evolution is a “powerful tool to understand the disease” and – importantly – can help us develop more rationally targeted treatments.

He also highlighted the power of gene sequencing to drive personalised treatment decisions for myeloma patients. Around 4 per cent of people with myeloma have faults in a gene called BRAF, and drugs are already available that target this fault. Through a UK-wide screening programme researchers found one myeloma patient with a BRAF fault who had already exhausted other available treatment options – their doctor put them on a BRAF inhibitor drug, and the patient is now in remission. Although only an anecdote, this story shows the difference an in-depth understanding of the genetic faults behind cancer can make in the fight against the disease.

Drugging the undruggable

Another of this morning’s sessions took a look at how we can use biology and chemistry to develop drugs that target so-called “undruggable” targets in cancer cells.

Many successful drugs are designed to lock onto enzymes – molecules that catalyse chemical reactions inside cells. Enzymes often have deep, interestingly-shaped ‘pockets’ that are perfect fits for drugs to block them. But the faulty proteins in cancer cells are often flatter and less distinctive. Furthermore, it’s also becoming clear that in many cases it’s the interaction between two molecules that’s important in cancer, not just the proteins themselves.

Four speakers – Martin Drysdale from our Beatson Institute in Glasgow, David Spring from the University of Cambridge, Guowei Fang from Genetech/Roche in California and Chun-Wa Chung from GlaxoSmithKline – outlined some of the challenges they’re facing in developing ways to “drug the undruggable”. From increasing the “shapeliness” of potential drugs to piecing together tiny chemical fragments to create new medicines, this session highlighted the future of cancer drug development.

Of particular note was Genenetch’s latest update on their efforts to target a protein called Ras (we covered this in outline here last year).

Accelerating the hunt for new cancer drug targets

“We’re at a watershed in cancer research,” according to Professor William Hahn, the 2012 conference’s final speaker.

Echoing a sentiment we’ve heard several times over last few days, Hahn pointed out how our molecular knowledge of cancer is now accumulating at an astonishing pace, but “we’re now generating a vast amount of data – way more than you can analyse in a spreadsheet.” We urgently need to find a way to turn this information into ways to beat the disease, he said.

Hahn’s lab, at the Dana-Farber Cancer Institute in Boston, has been engaged in a Herculean effort to systematically map out the molecular faults in hundreds of different strains of laboratory-grown cancer cells, study how they work, and then find out if these findings are relevant in actual tumours – a process called ‘integrated functional genomics’. Project Achilles, as it’s known, has already found some tantalising hits.

First, Hahn described how they’d found high levels of a molecule called ID4 in ovarian cancer, which seems critical for their survival. They’ve tried knocking this out in animal models using high-tech nanoparticles, with some success. They now need to find a way to see if this works in patients.

Another ‘hit’ from Achilles has been to tease out the role of a protein called YAP1 in bowel cancer. Again, this seems critical for bowel cancer cells’ survival, and blocking its interaction with another protein called YES1 also seemed a promising option. Again, this needs confirmation ‘in the wild’.

These are just tasters of the sort of work they’re doing by systematically working through cell lines and then validating the ‘hits’ in follow-up experiments. And they’re making all their data available to the research community online, to further speed up progress.

And finally

In his closing address, Professor Gerard Evan thanked everyone who’d made this fascinating and absorbing conference possible – particularly the hard-working conference staff who had to deal with a thousand odd delegates who, Evan quipped, “are quite frequently on the autistic spectrum, and certainly on the obsessive compulsive one, when it comes to social skills. But thanks to their brilliant work, not a single fight has broken out”.

So, that’s it for our round-ups from 2012’s NCRI conference. If you’re hungry for more, our very own Dr Kat Arney co-presented the Naked Scientists BBC Radio show live from the conference on Sunday night, featuring opening speaker Joan Massague, and a stellar cast of cutting-edge cancer researchers (as well as a talking elephant!). You can listen to the show for free from the Naked Scientists website. And we’ve got a couple of in-depth write-ups of two of the sessions still to come, so watch this space.

Henry, Olly and Kat