After yesterday’s talks, the first full day’s play at the NCRI Cancer Conference saw some excellent sessions on how the last decade of high-tech cancer research is beginning to affect how patients are treated.
Topics included drug resistance, national cancer statistics, the immune system, ‘stratified’ medicine, brain tumours and clinical trials.
Here’s how the day panned out.
To kick things off, Professor Jeff Settleman, from US research company Genentech, gave us a new take on an old problem – drug resistance.
So-called ‘targeted’ cancer therapies – the end-products of our new understanding of cancer’s inner workings – aren’t yet delivering their full promise in trials. The main reason, according to Professor Settleman, is that cancers appear much more “plastic” than previously thought, and cancer cells seem to have all sorts of tricks up their sleeve to escape attack from these new agents.
He dramatically illustrated what this means in practice with a series of three photos of a man’s torso. In the first, the man was covered in small lumps – the lethal hallmark of advanced melanoma. In the second, after 15 weeks treatment with vemurafenib – a promising new targeted treatment – he appeared completely normal: the cancer had melted away. But just 8 weeks later, the cancer was back, and his torso was once again studded with tumours. His cancer had adapted to the tiny molecular spanner thrown in its works, and begun to grow again.
Thanks to the latest lab techniques, scientists like Professor Settleman are learning exactly how this occurs – and how to stop it. In fact, researchers are unravelling some of the resistance mechanisms to these new drugs even before they’ve been fully tested.
Importantly, the ways in which cancer cells perform these escape acts turn out to involve molecules, such as Her2 and EGFR, that we’ve already developed drugs to target. Clearly, a huge part of the future of cancer care will be carefully designed combinations of treatments, coupled with routine genetic and molecular monitoring of a patient’s progress.
We’ll need collaborative and innovative trials to get there, but the future of cancer treatment is looking ever brighter.
Cancer: policy and politics
In what he admitted was “something completely different”, the Government’s National Cancer Director, Prof Sir Mike Richards, then shifted our attention from the future back to the present, and to the UK’s poor survival rates relative to ‘the best in Europe’.
According to a recent analysis in the British Journal of Cancer, Richards said, up to 10,000 premature deaths could be avoided every year in the UK if we closed this gap.
Professor Richards outlined the work he’d been leading to understand the reasons for this gap, and to ultimately close it. The Government, he said, was committed to a ‘hugely ambitious’ target of halving the gap by 2015, avoiding 5,000 premature deaths per year.
Some of the things that need to be done are well-known – for example improving the public’s low awareness of cancer symptoms. But for other areas – for example, GPs’ access to diagnostic tests and their willingness to use them – we still don’t know how we compare to other countries, and so can’t say what policy levers to pull. Thankfully, the International Cancer Benchmarking Partnership is set to answer many of these questions, and guide our policymakers to the way forward over the coming years.
After a quick coffee break, we split into several different in-depth sessions. We were at a session on stratified medicine – the grouping of patients for different treatments according to the molecular characteristics of their tumours.
Chaired by CEO of the Institute of Cancer Research, Professor Alan Ashworth, the session began with a look into the future – when many cancer doctors and researchers hope it will be possible to choose the right treatment for each patient, based on a better understanding of each person’s cancer. This is already happening with some types of cancer up to a point, but there are some huge challenges ahead before we reach truly ‘personalised’ medicine.
First Professor Alberto Bardelli, from the University of Torino Medical School in Italy, explained the advantage of investigating genetic changes using a simultaneous, three-pronged approach – studying cells in the lab, testing drugs in mice, and running clinical trials in humans.
Investigating changes inside cancer cells gives clues for which drugs could be suitable for certain patients, and then this can be confirmed in mice. This information is used in real time to guide clinical trials in patients, and running these stages in parallel is really speeding up research.
Next Professor Jean-Charles Soria from the French Institute Gustave Roussy, explained his latest work into tailoring treatments for lung cancer. There are already some drugs available that target particular changes in lung cancer cells, and he outlined his hope for the future, when all lung cancer patients will have ‘molecular portraits’ produced to show the exact changes in their cancer cells. These portraits will determine their treatment, and should help to save more lives.
Finally David Gonzalez do Castro, from the Institute of Cancer Research’s molecular pathology division at the Royal Marsden Hospital in Sutton, tackled one of the biggest hurdles in stratified medicine. We now have huge amounts of data about the genetic changes that are common in certain types of cancer, but we urgently need ways to test for these changes in patients and work out how they affect treatment.
He emphasised that these tests need to be reliable, economic, quick to perform, and should be fully embedded in of the normal process of diagnosis. We were delighted to see Cancer Research UK’s own Stratified Medicine Programme held up as a great example of how work is progressing to work out how to bring these tests to patients.
After half-time break for lunch, the day’s second half began. We went to a session on immunotherapy – a fascinating area of research that aims to harness the immune to tackle cancer.
We heard from three major players in the field, with exciting news on the progress they’re making.
First, Professor Adrian Hayday of our own London Research Institute explained how immune cells can sense damaged cells and destroy them before they develop into cancer. This amazing natural protection evolved as a way to defend the body against invading bacteria, before being co-opted to help protect us against ourselves. The hope is it that it can be further harnessed to help treat certain cancers.
Next Professor Bob Schreiber from the Washington University School of Medicine turned things on their heads, discussing how the immune system can actually help cancers themselves to evolve. Immune cells, it seems, can detect certain cancer cells and destroy them, but other cells in the cancer are less readily spotted.
Over time these cells that ‘fly under the radar’ are left behind, so the cancer gradually becomes invisible to the immune system and can grow and start to cause problems. But there may be a way to help the immune system recognise these ‘invisible’ cells and kill them, harnessing the power of the body’s own defences.
Finally, Dr Jerome Galon from the French National Institute of Health and Medical Research (INSERM) explained how monitoring a patient’s immune response to cancer can actually predict how their disease will progress. Research into bowel cancer has shown that measuring the proportion of immune cells inside a tumour can give a really good indication of how long a patient will survive.
Indeed, this seems to be better than the traditional, tried-and-trusted method of seeing how far the tumour has spread and what the cancer cells look like. This exciting research could help to decide which patients should receive particular treatments – again, hinting at a more ‘personalised’ way to treat cancer.
Focus on brain tumours
We then headed off to a session on the management and treatment of brain tumours, which gave an insight into the new approaches that are being used to tackle this hard-to-treat group of diseases.
Survival rates for brain tumours remain poor in adults, with a better outlook for children, and there is still much that needs to be done to improve treatment across all ages.
Dr Roeland Verhaak, from the MD Anderson Cancer Center in the US, described how the wealth of information about a form of brain cancer called glioblastoma coming out of the Cancer Genome Atlas project has revealed over 180 gene faults that may be involved in the disease. Most of these faults are rare, so the challenge is to unravel their individual roles in the disease – but the scope of this project holds great promise.
Then, Professor Steve Clifford of Newcastle University revealed how treatment for children with another brain cancer – medulloblastoma – might be further improved by using gene analysis to determine the course of treatment. This is currently being explored for the first time in this cancer in two European clinical trials, PNET5 and PNET6, involving a large proportion of UK patients.
Finally Dr Martin Taphoorn from the Medical Centre Haaglanden, in the Netherlands, reminded the audience of the neurological side-effects of brain tumours and their treatments and explained how these difficulties make a patient’s quality of life hard to measure, in a way that is unique to these cancers.
The challenges remain, but the session reminded us of the incredible imagination researchers around the world are using to make a breakthrough for brain tumour patients.
Latest clinical trials
The day’s final session was a clinical trials ‘showcase’ – always a highlight of the conference for doctors at the sharp end of treating cancer patients. Amongst this year’s presentations were exciting results from trials of new drugs for prostate cancer, melanoma, and Dr Indrajit Fernando talked about the outcome of SECRAB – a Cancer Research UK-funded trial looking at the best timing for giving chemotherapy and radiotherapy to women with early breast cancer.
We covered this story on our news feed in September, when the trial results were first revealed, but it’s worth mentioning Dr Fernando’s closing words to the audience at the conference.
After giving heartfelt thanks to Cancer Research UK and the National Clinical Research Network for making the study possible, he reminded everyone that SECRAB didn’t involve any expensive new drugs or treatments that aren’t currently available to patients everywhere in the UK. The trial showed that just changing the relative timing of when patients receive chemotherapy and radiotherapy could make a small but significant difference to the chances of breast cancer coming back – and that could add up to saving the lives of many thousands of women over the coming years.
After the day’s early sessions looking to the more personalised future of genetic medicine, it was a sobering reminder that, while some are working hard to usher in a new era, others are making an important difference to cancer patients by incrementally improving what we already have.
Henry, Kat, Nell and Julie