Notes from the NCRI conference (day 3)

It’s been another packed day at the NCRI conference, full of interesting discussion and debate (as were yesterday’s and Sunday’s sessions).

But before we get stuck into the day’s events, it’s worth flagging the overnight media coverage from the meeting, with OnMedica covering this story on prostate screening, while the BBC was one of several news outlets to cover a promising potential method to detect cancer.

And now to the main event.

Breast screening review

The day’s proceedings began with a packed session discussing the results of the recent Independent Breast Screening Review, which made headlines around the world last week.

Our chief executive, Harpal Kumar, kicked off proceedings with a recap of the rationale behind the review, after which panel member Professor David Cameron (no relation) presented its findings – quantifying screenings risks and benefits – in a superbly lucid and clear manner.

The final Q&A session was absorbing, with a highly engaged room of delegates eager to put across their points of view. And Professor Sir Mike Richards – the National Cancer Director for England, announced that the NHS breast screening leaflet is currently being reviewed by a team containing Professor Amanda Ramirez and top statistician Professor David Spiegelhalter, which is great to hear.

You can find our summary of the Review’s findings on our main website.

Hunting for genetic cancer risk – where next?

A person’s risk of cancer is a complex mix of genetic and lifestyle factors. Over the last few decades, researchers have tried to pin down the nature of our genetic risk of cancer by carrying out so-called ‘genome-wide association studies’, which have highlighted regions of our DNA called SNPs that affect an person’s risk of cancer.

The morning’s second session – chaired by the director of our Cambridge Research Institute, Professor Bruce Ponder – looked back on this research, and asked: where next?

First up, leading cancer epidemiologist Professor Paul Pharoah asked whether we’ve come far enough in understanding ovarian and breast cancer genetics to change how we manage these diseases. We’re some way from this with ovarian cancer genetics, which “isn’t yet ready for prime-time,” according to Pharoah.

But he thinks that the time is right to begin a national randomised trial of breast screening, where women whose genes suggest they’re at low risk are offered the chance to be randomly allocated to either be screened or not. This, he thinks, would answer many of the questions that the recent breast screening review wasn’t able to answer.

Pharoah was followed by his colleague Professor Julian Peto, who pointed out that the explosion in knowledge of cancer risk genes hasn’t yet been matched by an increase in understanding how they affect risk. This is vital, he argued, if we’re to turn knowledge into patient benefit.

One example, he said, was the discovery of a SNP that reduced the chances of smokers developing a form of lung cancer by about a fifth. We urgently need to understand this “profound and powerful” effect. He also highlighted the need to find variants that increase risk among the young.

The final presentation came from US expert Professor Andrea Califano. Although his work doesn’t focus on cancer risk itself, it involves looking for patterns in biological systems and data, and he suggested that cancer geneticists like Ponder, Pharoah and Peto could usefully exploit these techniques. He also pointed out that his recent work on how a molecules called RNAs can help regulate genes could explain some of the variation in cancer risk between individuals.

From despondence to hope

Lung cancer has historically been viewed as incredibly difficult to treat – it’s often detected late, grows fast, and has very poor survival, with only three in 10 patients surviving for even one year after diagnosis. And because smoking causes most cases, patients often have other smoking-related diseases such as heart disease and COPD, causing complications with cancer treatment. But the mood is slowly changing.

As session chair Dr Fergus Macbeth pointed out to the packed room at the start of today’s lung cancer session, just a few years ago the room would have been only half full. Lung cancer has seen a recent surge of interest from doctors and scientists, and new drugs and radiotherapy techniques are starting to make a difference to patients.

First, Dr Frances Shepherd from the Princess Margaret Hospital in Toronto talked about the challenges of working out how faults in genes such as EGFR and KRAS affect a tumour’s response to chemotherapy, and the search for the “Holy Grail” of lung cancer – a molecular test that can accurately predict which patients need which therapy, and how well they’re likely to do.

She was followed by Dr Kevin Franks from St James’ Hospital in Leeds who discussed the potential benefits of more accurate forms of radiotherapy, known as SABR or SBRT (often referred to by it’s brand-name – CyberKnife), for treating lung cancer.

Finally, Cancer Research UK-funded Dr Corinne Faivre-Finn talked about the challenges of using higher doses of radiotherapy to treat lung cancer. But although bigger doses are more effective at treating tumours, they also lead to more side effects, so more isn’t always better.

We’ve still got a long way to go to make meaningful improvements in lung cancer survival, but it feels like the international research community is moving together in the right direction.

How healthy cells contribute to cancer

Cancer Research UK’s Professor Margaret Frame chaired a highly technical but fascinating morning session about the interaction between tumours and healthy cells in the body – another hot topic in cancer research. Tumours, we now know, don’t just exist in isolation but can co-opt healthy tissues to help them grow, spread and resist treatment.

Professor Frame described how ever-more sophisticated technology and research techniques are fuelling an explosion in our knowledge of how the so-called ‘tumour microenvironment’ is involved in cancer. This was particularly evident from Dr Jacco van Rheenan’s talk. Dr van Rheenan, from the Hubrecht Institute in The Netherlands, wowed the audience with his videos tracing the growth and spread of tumours in real time.

He’s found that different areas of tumours have different growth characteristics, with some sections growing constantly, while others grow and then regress. This might indicate that tumour cells switch between different behaviour states, and can gain or lose the capacity to fuel tumour growth. Theoretically the most effective treatments should target the tumour-fuelling cells.

His team have also closely monitored the movement of cells within tumours using advanced microscopes combined with lasers that activate glowing markers in cells. When close to blood vessels, the tumour cells moved a lot more, which is interesting as tumours can spread to other parts of the body through such vessels. The research also indicates that there are many more immune system cells called T-cells where there’s more tumour cell movement. Even more intriguingly, using antibodies to get rid of these T-cells hugely decreases this movement.

Dr van Rheenan said “we have no idea why this is happening, but we now have a powerful tool to investigate the tumour microenvironment”. Will future cancer treatments exploit this knowledge to stop cancers spreading? Only time will tell.

Early diagnosis of breast cancer

In the afternoon, we heard a great round-up of new research into early diagnosis, including a star turn from Cancer Research UK’s Professor Ian Jacobs, who’s running a study looking at whether testing whole populations for the cancer-causing faults in the BRCA1 or BRCA2 genes could help identify more people at high risk of cancer, so they can have tailored screening or prevention.

The Ashkenazi Jewish population has a particularly high chance of having these mutations, which gives women about a 45-65 per cent chance of developing breast cancer, as well as a host of other cancers.

People in the trial were put into two groups: one was offered genetic testing only if they had a long family history of cancer, and the other group were all offered testing, no matter what their family history was.

Screening the whole population seemed to be more effective. About half the mutations were picked up in people without a family history of cancer, and all these people would be missed if screening stayed the same as it is now. And even for the mutations in people with a family history, Professor Jacobs calculated that it’d take more than 40 years to find them all.

He suggested that in this population at least, everyone should be offered genetic testing, no matter what their family history is. Whether this would work in groups with a lower chance of having the mutation remains to be seen, but for the Ashkenazi Jews at least, this approach could make a real difference.

Cancer evolution

Picking up where yesterday left off, another session was devoted to this year’s Zeitgeist topic – cancer’s ability to evolve. UCL’s Professor Tariq Enver, led the discussion of how this happens and what drives it.

A crucial question for researchers studying cancer evolution is how it fits together with another ‘hot topic’ in cancer research – the idea that cancers are driven by defective ‘stem cells’ that fuel the production of new cancer cells.

The first speaker was Professor Cedric Blanpain from Belgium, who discussed his work on stem cells in squamous cell cancer – a form of skin cancer. His lab has shown that these cancers are – like others – made up of diverse populations with different characteristics.

Next, Canadian research Peter Dirks outlined his lab’s extraordinary work on glioma brain tumours . Again, it turns out that these tumours are made of distinct populations, differing in their ability to grow, divide and start new tumours.

Finally, our own Professor Charlie Swanton recapped – and elaborated upon – his landmark kidney cancer paper from earlier this year, discussing the challenges and opportunities that this intratumour heterogeneity presents. Harking back to Carlo Maley’s talk yesterday, Swanton suggested that diversity appears to be a useful marker for how advanced a tumour is – and that this could guide treatment choice.

On top of this, Swanton pointed out that the mutations in the ‘trunk’ of a tumour’s evolutionary tree should provide excellent drug targets if we can pin them down. And he showed how detailed analysis of a patient’s tumour could reveal potential treatment avenues, but how this, currently, was happening too slowly.

“We’re behind the curve – regulatory, bioinformatic and validation hurdles are longer than median survival times,” he said, after presenting data of a brain tumour patient who died before information on her cancer could be fully analysed. It was a sobering demonstration of how far we have to go, despite the undoubted promise this research is generating.

Cancer cell death – whodunnit?

In an intriguing afternoon session, chaired by Cancer Research UK scientist Henning Walczak, three speakers discussed their work on understanding the mechanisms by which cells die.

In particular, it was fascinating to hear about a recently discovered cell death mechanism, called ‘necroptosis’. Scientists are now developing drugs that can switch on necroptosis, and lab tests show that these molecules can kill cancer cells that have learned to ignore the usual ‘death wish’ signals.

First, Peter Vandenabeele (University of Ghent) presented his work on discovering the brakes and gears that either stop or drive cells to their death.

Next, Pascal Meier of the Institute of Cancer Research showed how his lab are studying a group of molecules in our immune system that act as release switches for cell death, which means that a drug that can open the switch in tumours will kill these cells.

And finally, Douglas Green of St. Jude Children’s Research Hospital in the US – a loud man with even louder shirts – explained his lab’s work on the interplay of factors that help embryos develop normally as well as triggering cell death when needed, and how cancer cells hijack these signals to survive.

All of this work will help scientists design better drugs that, when used together with other therapies, will attack cancer cells on all fronts and, hopefully, stop tumours coming back.

There’s just one more day of this fascinating conference left – we’ll be back tomorrow to report on how it went.

Henry, Kat, Olly, Jess and Matt