NCRI 2014 conference summary – day 3

A look through the morning’s media coverage surfaced these reports from the conference:

• This story about emergency lung cancer diagnoses appeared in the Times.
• New results on how swallowing a ‘sponge on string’ could replace endoscopy to diagnose oesophageal cancer appeared on the BBC news website.
• And this article from the Mail Online featured a presentation from Professor Sir Mike Richards that we covered yesterday.

Tackling brain tumours

Dr Luis Parada kicked off the day’s talks with fascinating insights into how brain tumours develop and how we might be able to stop them.

He said, “We cannot just look at how cancer ends – we need to know how it begins.” Brain tumours typically start with specific gene faults in stem cells of the brain. Parada explained that these cells grow slowly but can go on to produce much faster growing cancer cells. The problem is that these stem cells are often missed by cancer treatment and can be the reason tumours return after treatment.

Parada’s team, based at the University of Texas Southwestern in Dallas, tested over 200,000 potential cancer drugs in mice and found a handful that killed the stem cells while leaving healthy cells unharmed. Dr Parada is now searching for the targets of these drug to “reveal the fragile underbelly of the cancer cell”.

Trial by basket

Today’s installment of the excellent “10 year celebration talks” kicked off with Professor Andrew Hughes, from our Lung Cancer Centre of Excellence, who spoke about how clinical trials are changing and what he imagines the future of trial design will look like.

Following on from yesterday’s talks on circulating ‘markers’ of cancer, Hughes outlined the potential for switching from taking samples of a patient’s’ tumour to so called “virtual biopsies” from blood samples. In the future, such tests could reduce the risks associated with taking tissue samples for some cancers and may provide doctors with more regular, detailed information on the patients disease.

Hughes spoke about the importance of collaboration between different organisations for new, large scale trials – dubbed ‘basket trials’ – that, based on the genetic signature of patients’ tumours, will determine which drug different groups of patients receive from an array of targeted treatments. And Hughes gave a nod to the national lung MATRIX trial, which we are funding, citing it as a “terrific exemplar” of how such studies could be done.

Finally, Hughes outlined some fascinating new technology to capture patient information during a trial, for example, by patients recording a video to describe their experience on smartphones.

High-energy research

The second of the day’s celebratory talks came from Professor Karen Vousden, director of our Beatson Institute in Glasgow who focussed on “metabolomics.” For the uninitiated, metabolomics is the study of metabolism – how cells create and use energy, and how this feeds into the development and potential treatment of cancer.

To start, Vousden pointed out that “none of this is new”, harking back to 1923 and the work of Nobel prize-winning German scientist Otto Warburg. He noticed that cancer cells use glucose (a type of sugar molecule) to make energy in a different way from healthy cells, without having to use oxygen. Although Warburg’s observation was extremely important, and still relevant today, there were many aspects of cancer metabolism that he didn’t understand. (As an aside, Vousden pulled out a fascinating example of Warburg’s straightforward approach to writing scientific grant applications – a single sentence reading “I require 10,000 Marks”).

She then went on to cover some fascinating new research from her lab suggesting that a diet low in the chemicals serine and glycine (two of the molecular ‘building blocks’ of proteins) might help to control cancers, at least in mice that have been genetically engineered to develop bowel tumours and certain other cancers.

Keeping it local

Professor Tim Maughan closed the session by outlining the changing face of surgery and radiotherapy, which, as Maughan points out, “cure more cancers than any other type of treatment.”

Maughan illustrated that with surgery, less is more. Over recent years we have been steadily moving towards better surgery techniques that are less invasive – meaning patients experience fewer complications and recover faster. Robotic surgeons may seem like something from a science-fiction film but human surgeons are in fact already using robots to help in their surgical procedures. Maughan predicted that we will increasingly turn to these robots and high-tech imaging techniques to more accurately and completely remove tumours.

Moving to the future of radiotherapy research, Maughan highlighted emerging improvements in the precision of radiotherapy over the last 30 years. The promising future for radiotherapy will feature sophisticated imaging, new technologies and highly complex computer programmes to focus the radiation beam on a tumour, sparing healthy surrounding tissue and minimising side effects, ushering in what Maughan sees as “a new paradigm in localised therapy.”

Unleashing the immune system

A session on immunotherapy explored how the power of the immune system can be harnessed to attack cancer. The take home message from the session was simple: use drug combinations.

According to Dr Christian Blank, by using more than one drug we can “loosen the brake and push the throttle” on immune cells – and in doing so make them better at killing cancer cells. He presented results from early stage clinical trials showing that targeting PD1, PDL1 and CTLA4 – molecules present on the surface of tumour cells and immune cells – at the same time killed more cancer cells.

Dr Sergio Quezada shook things up by showing how the recently developed drugs that target PD1 and PDL1 (something we’ve written about recently) could be working differently to what we think.

And Dr Adrian Hayday shared data that could one day lead to new treatments for melanoma by developing drugs that release an army of tumour-attacking immune cells – known as T cells – trapped in a particular part of skin.

Living with and beyond cancer

At a session on optimising care for those living with and beyond cancer we heard about several research studies exploring the role of primary versus secondary care.

Of particular interest was research looking at conditions that cancer patients may go onto develop, such as a new and different form of cancer, osteoporosis, and cardiovascular disease.

Interestingly, in the the US, an entire new discipline is evolving looking at those cancer patients who go on to experience cardiovascular disease – known as ‘cardioncology’.

Cancer evolution – it’s all about the trunk

Although it was first documented in 1976, the way tumours evolve has recently been the subject of intense scrutiny. Two years ago, the topic took up a relatively small session in a side room at the NCRI conference. This year, Cancer Research UK’s Professor Charlie Swanton chaired a session in the huge main hall here at the BT Convention Centre.

First, computational physicist Andrea Sottoriva, from the ICR Centre for Cancer Evolution, talked about his team’s recent insights into bowel cancer evolution. They think they can explain the patterns of mutation they see in samples from patients by analogy to the ‘Big Bang’ at the dawn of the universe. “If everywhere you look, you see heterogeneity”, he said, then the “simplest explanation” is that heterogeneity was there from the beginning. In other words, these tumours were “born to be bad”.

Next, Nicholas McGranahan from Swanton’s lab talked through their recent research on lung cancer, which we discussed in detail when it was published in October.

And finally, Scott Carter from the Broad Institute in the US, explained how his team are developing high-powered software to analyse the genetic data within tumours and construct their evolutionary history. He showed some incredible – and somewhat depressing – results of studies of cancers that have spread to the brain. It turns out that these can be radically different from the original (primary) tumour – so much so that the treatment decisions made after analysing the DNA of the primary are, in retrospect, wrong. The solution? As with so many talks at this year’s conference, the need for ‘liquid biopsies’ of circulating tumour DNA , that can properly represent what’s going on in a patient’s cancer.

Melanoma cells lend a helping ‘hand’

Dr Pippa Corrie introduced a fascinating session on melanoma, focusing on the potential of targeted treatments.

Two fascinating talks showed how ageing and the environment affect melanoma at the cellular as well as the population level. Dr Ashani Weeraratna showed how the cells and molecules found in ageing skin can actually help melanoma cells to survive and spread – perhaps explaining why older patients don’t respond so well to the new generation of targeted drugs. This poses a tantalising question of how excessive sun exposure could be ‘ageing’ the skin at the microscopic level as well as cosmetically.

And finally Dr Claudia Wellbrock showed how groups of melanoma cells that are more resistant to targeted drugs can actually help protect more sensitive cells in the same tumour, through cellular communication. Exciting early stage work suggests this process could potentially be blocked by combining targeted melanoma drugs with an existing HIV drug called nelfinavir.

How do cells respond to radiation?

A session on radiotherapy highlighted the exciting research that is going on in understanding how cancer cells respond to radiation and crucially how we could exploit this to make treatments like radiotherapy more effective. “Radiation is a form of active immunotherapy” said Professor Kevin Harrington, highlighting that radiation can also provoke an immune response to cancer cells and should be an area we look into more.

Catastrophic damage

Dr Chris Lord of the Institute of Cancer Research (ICR) introduced talks on the theme of DNA repair and cancer. As a disease of faulty genes, DNA damage — or the lack of effective repair — is an important part of the development of cancer. This has long been exploited in treatment, as inducing catastrophic DNA damage can prompt cancer cells to self-destruct. The speakers described some surprising new research in the process.

Dr James Knight described a method for using PET imaging to picture DNA double strand breaks — and so, we hope, monitor how tumours are responding (or not) to treatments which induce DNA damage. Dr Reuben Harris from the University of Minnesota told us about APOBEC3B, an enzyme which was recently shown to cause DNA damage and which is associated with poorer outcomes in breast cancer.

But the showman of the session was Professor Johann de Bono of the ICR and The Royal Marsden hospital. He briefly reviewed the amazing progress we’ve seen in prostate cancer treatment in the past decade — one of his patients was “sent home to die” in 2003, but he responded brilliantly to a series of trials of several new drugs which have since been introduced on the NHS. He’s still alive today. The latest of those drugs was Olaparib, one of several exciting new drugs which block DNA repair enzymes called PARP, and de Bono then talked about the great results they’ve been getting with PARP inhibitors in BRCA mutant prostate cancer. You can read more about the drugs here.

Clinical trial showcase

We’ve heard about several exciting clinical trials during the conference and a fascinating example of a trial looking to improve the diagnosis of cancer was presented by Professor Rebecca Fitzgerald. The ‘cytosponge’ – sometimes referred to as a ‘sponge on a string’ – has been designed to detect a disease called Barrett’s Oesophagus (which can develop into oesophageal cancer).

The trial has shown that this test, which uses an expandable sponge to collect cells from patients’ oesophagus, is effective at detecting the disease. Fitzgerald, lead investigator on the BEST2 trial also said that the trial found the test was “very safe” and “acceptable to patients.”

The test could be used in GPs surgeries as a simply way to identify patients that need to go for further tests in hospital.

Seeing is believing

Professor Margaret Frame, from our Beatson Institute in Glasgow, closed the day’s talks with an in depth story about how an important molecule that some cancer cells produce in excess – called focal adhesion kinase, or FAK for short – interacts with the immune system in mice with skin cancer.

Frame presented a fascinating series of experiments going from a “serendipitous” discovery of the links between FAK and the immune system to early data about how FAK could become a target for treatment in the future. The team treated mice with a drug – which is also going through early stage clinical trials – that switches off FAK, and this was able to reawaken the immune system and shrink the tumours.

Frame says “seeing is believing,” and the striking images of cancer cells and the world around them that her lab produces were a stunning way to end the day.