NCRI 2014 conference summary – day 1

Over the next few days, the National Cancer Research Institute’s annual conference is taking place in Liverpool – and this year is a special year: it’s the conference’s 10th anniversary.

And as in previous years, we’re here at the conference to bring you daily updates of all the news and developments.

But before we arrived in Liverpool, there had already been some media coverage of research being presented at the event:

• this story about a ‘self-destruct’ switch in lung cancer cells was covered by the Express and the Mirror
• this story about ethnic minorities being less aware of cancer symptoms was picked up by the BBC
• and research about early diagnosis of children’s cancers was mentioned on the Today programme on BBC Radio 4

A winning combination?

And so to the day’s proceedings. After a brief introduction and welcome from the NCRI Director, Dr Karen Kennedy, it was time for some science. Introduced as a scientific “superstar”, Professor Lewis Cantley kicked things off with a whistle-Dstop tour of research on a key molecule linked to the growth and survival of cancer cells – a protein called PI3 Kinase (or PI3K for short).

Since he discovered the molecule in 1985, Cantley and his team have been looking to find new ways to target PI3K to treat cancer.

Presenting their latest research, Cantley showed that switching off PI3K in mice with a form of triple negative breast cancer stopped the tumour cells from producing a chemical called ribose, one of the building blocks of DNA – which led to them having problems dividing and causing damage to their DNA.

By combining drugs that switch off PI3K with another type of drug called a ‘PARP inhibitor’ – which our scientists played a key role in discovering and developing – they were able to ramp up lethal levels of DNA damage in the cancer cells, causing the tumours to shrink dramatically in mice. The team are now testing this drug combination in early stage clinical trials in women with triple negative breast cancer and ovarian cancer.

A risky business

An energetic talk from David Spiegelhalter, Winton Professor of the Public Understanding of Risk at the University of Cambridge, and self-confessed ‘performing statistician’, followed – with a timely reminder that “numbers and the media often don’t get on.”

In a whirlwind tour, taking in the good, the bad and the ugly of health communications, Professor Spiegelhalter introduced various concepts and methods for pesenting numbers, including different ‘framing’ (e.g. stating the number of people who live, rather than the number who die), and representing risks in pictures and diagrams.

But risk is everywhere, and we were also introduced to the somewhat startling idea that watching Downton Abbey increases your risk of death by 9 per cent – but only if you watch it every night of your life. This wasn’t a reference to Julian Fellowes’ plotlines, but rather to the risks of spending long amounts of time sitting, which we’ve blogged about before.

But what does a 9 per cent, or indeed any other, ‘increased risk of death’ really mean?

Spiegelhalter presented several ways to communicate this, including the concept of the ‘microlife’. These are based on the idea that one year of extra life is roughly equivalent to an extra 30 mins of each day, and break long-term risks down to a daily, more easily understandable level.

So watching two hours of Downton Abbey every day would cost one extra microlife (on top of the 4 someone might spend watching it). And for people who smoke, every 2 cigarettes a day costs them one microlife.

But some things add microlives – the first 20 or so minutes of physical activity you do a day gives you back more time than you invest.

And other lifestyle choices are more complicated – alcohol for example. One drink a day can cut your risk of death – mainly through effects on heart disease – but as Spiegelhalter put it, after that point it’s “poison, poison, poison.”

Numbers are important: they’re part of the stories of our lives, and we need to think about how they’re communicated.

As Professor Spiegelhalter put it, “if we want to be honest, transparent and good at communicating science, we need to be balanced”.

How to treat different types of lymphoma

Following this thought-provoking talk we were back to cancer research proper, and Dr Louis Staudt, from the US National Cancer Institute. His talk focused on one of the less common cancers – diffuse large B-cell lymphoma – and the search for the “genetic smoking gun” driving different forms of this disease.

It’s become clear in recent years that this cancer falls into two distinct genetic subtypes, known as ‘ABC’ and ‘GCB’, each driven by different faulty genes, and responding to treatment in different ways.

In particular, Staudt and his team are focusing on a new targeted drug called ibrutinib. Lab studies have suggested that it might be effective against the ABC form of the disease, and this turned out to be the case in early stage clinical trials. Staudt highlighted one patient whose cancer was completely cured by ibruitinib, and she remained cancer-free more than four years later. But although, as he described, this was a “wonderful success”, this patient was very much the exception rather than the rule.

However, a larger trial did suggest that ibrutinib could be promising for people with this ABC form of diffuse B-cell lymphoma. Unfortunately, certain mutations in key genes can make tumours resistant to the drug, either straight away or over time as the cancer evolves. Staudt and his team are now working to understand some of these gene faults, as well as how the immune system interacts with the cancer cells, to find better ways of targeting these lymphomas.

But it looks like these treatments will need to be used in combination rather than one at a time, in order to overcome drug resistance – something that can be difficult to trial when drugs are made by different companies. According to Staudt, “every lymphoma is a different story” in genetic terms, but by understanding the key plot lines, there is hope that more effective treatments will soon be on the way.

Breast cancer debate

After a short break, the conference split into two groups – one focusing on drug development, the other a debate – hosted by Breakthrough Breast Cancer – on whether so-called ‘genomic medicine’ in breast cancer is ‘hype’ or ‘reality’.

This proved to be a highly entertaining, rumbustuous 90 minutes. One side, led by Professor David Cameron (no relation) from the Edinburgh Cancer Centre maintained that the ability to analyse the genetic make-up of a woman’s breast cancer is bringing real, tangible benefits to patients already.

The other, let by Dr David Miles from Mount Vernon Hospital, argued that we still have a long way to go to understand cancer’s fearsome complexity – the integration of this into routine care is still a way off. We’ve written before about these challenges and how researchers and policy makers are trying to overcome them. (And you can read Breakthrough’s write up of the debate here).

Trials and tribulations

Turning to clinical trial design, Drs Sarah Halford and Gary Acton from the Cancer Research UK Centre for Drug Development (CDD) hosted a fascinating series of talks on the changing nature of early phase clinical trials.

Traditionally, ‘early phase’ trials were designed to determine how safe a new drug was for patients, with little information on how well it might work. But in the face of the “exponential explosion” in potential cancer drugs, and with more information being asked from early phase trials, the CDD has created a new drug development plan for the future.

Thanks to the accelerated pace of biological research, Acton, senior medical advisor to the CDD, said there were now “Too many drugs, too many potential combinations and too few patients to try them all.”

Much like supermarket sweep, where shoppers have limited time to bag as many groceries as they can and get the best deal possible, the CDD must forget running a trial for every possible new treatment and focus on the drugs that have the most promise for patients.

Following the mantra from T.S. Eliot “The end is where we start from”, the new CDD plan focuses on what treatment for patients will look like at the end of development, and designing the early phase trials to get there as quickly as possible.

That’s all for our Sunday round-up – we’ll be back soon for a run down of Monday’s happening’s.