Our blog from the second full day of the NCRI conference in Liverpool.
The day began with a selection of talks about the likely future of important cancer topics. First up was Andrew Hughes from pharmaceutical giant AstraZeneca. He took a look back at the recent history of clinical trials and the testing of new treatments in patients and gave us some insight into what we can expect from these in the future.
There will be blood
These sorts of biopsies can be done anywhere, which also opens up the possibility of trials that use these approaches happening in many more locations than those that rely on the physical biopsy. So is the virtual biopsy science fiction? No. AstraZeneca have submitted a proposal to avoid physical tumour biopsies for lung cancer, and move to blood tests instead. And the results so far suggest it's much better for patients. If nothing else the turnaround times are much shorter than for processing traditional biopsies; four days versus two weeks respectively.Clinical trials used to be based on a physical biopsy, where a small sample of the tumour is collected from the patient. Taking a physical biopsy carries some degree of risk for patients due to the invasive nature of the procedure. And these sorts of more traditional biopsies don't sample the whole of the tumour, just a small piece of it. We know that tumours are incredibly varied so that little chunk may not be representative of the whole tumour. That's where the virtual biopsy comes in. Taking a sample of blood and looking at the stray tumour material it harbours should be able to tell us much more about the tumour and be much less invasive for the patient.
Andrew mentioned other progress in clinical trials, including moving from testing just one treatment to trials where multiple treatments are tested simultaneously. And finally he talked about the data capture during clinical trials. Traditionally done through laborious computer processes, it would seem that the future is smart devices. The computer-based approach is long and inefficient, the patient has no voice and there’s no opportunity to adapt the trials as they go along. Andrew said that using smartphones instead will give immediate patient insight and voice and streamline how trials are monitored so they can be stopped or adapted very quickly.
Then we heard a fascinating talk by Karen Vousden about cancer metabolism - the way cancer cells create their energy. When things go wrong with our metabolism it can contribute to cancer. But this isn't new knowledge. The Warburg effect was proposed in1923 and it described how tumour cells use a different way of generating energy through a different metabolic pathway
Karen talked through a few experiments that showed the amino acid serine, one of the building block of proteins, is very important for cancer cells to survive. But can we use this information in cancer therapies?
In mice the answer is yes. Karen described experiments where mice were fed a special diet lacking serine. And just to make sure the mice still liked the food, it was made with their favourite flavouring - bacon. The mice can not only survive without serine in their diet but this special serine-free food also halted tumour growth in the mice.
But is it going to be possible to remove serine from human patients' diets? Probably not, so we may have to try and block serine being taken up from the diet instead. But before you rush out to find some supplements that lack serine, it's worth pointing out that this was only studied in a few mice so far. And even then not all types of cancer responded. So we don't know if this will benefit, or harm, human patients with breast cancer. But it's an interesting area of research to follow.
This time it's personal
This session of talks was rounded off by Tim Maughan who spoke about localised therapies - treatments specifically targeted at the tumour - and how we can expect these treatments to develop over the next few years.
Every cancer is unique and evolving, which makes each and every cancer very varied. This presents major challenges to personalised medicine and also makes resistance to these sorts of treatments inevitable. Using drugs that target a common skin cancer faulty gene, Braf, as an example, Tim said: "It took nine years to develop the Braf inhibitor but only nine weeks for the tumour to overcome it."
Tumour evolution takes place over many years to develop this complex level of variation. So if we could find the tumours earlier when they are less varied, we would stand a better chance of using surgery and radiotherapy to eradicate the cancer, hopefully avoiding the problems associated with resistance.
Tim mentioned that new types of radiotherapy, such as proton beam therapy, could make a big difference to women with breast cancer. Targeting the radiation specifically at the cancer means that we're more likely to avoid accidental damage to the heart that can happen with other types of radiotherapy. Tim suggested that in the future this could prevent many deaths from breast cancer.
Mapping tumour evolution
In the afternoon session we heard some rather mind-expanding talks about tracing the genetic life of individual cancers from conception to development of tumours and then to its spread around the body. Andreas Sottoriva brought a new angle to the conference by laying out how methods more associated with particle physics experiments are being used to understand how tumours evolve - in a theory he called the “Big Bang theory of tumour evolution”.
His talk showed how mutations responsible for the initial transformation of a normal cell to a cancer cell occur very early on in the life of the disease and drive the development of genetic diversity in a tumour. It’s this diversity that causes drugs to stop working in some patients and for tumours to return after a period where the patient may appear to be cured. Andreas stated that these mutations appear so early in the cancer’s life that it’s in a stage before the disease is detectable, leading him to comment “some cancers are born to be bad”.
GPs don't get up in the morning to miss a cancer diagnosis
The presenters began this session by outlining the common misconceptions about the problem of diagnosis. It's commonly believed that the problem is unique to cancer, unique to the UK and all about GPs. Their overarching point was that these are untrue. It's much more complicated than that.
One key and complex problem is the delay in the diagnosis of cancer. There can be delays when the patients don't seek help promptly, there can be delays at the initial presentation of symptoms at the doctor’s, and delays in getting the cancer diagnosed through referral to hospital. GPs are only part of this complex problem and there’s no single way to fix it.
Delays in diagnosis also arise when doctors miss the signs of cancer during a check up. But how often does this happen? The speakers stated that 82 percent of cancers are diagnosed after just two consultations with the GP. This is pretty good as diagnoses go, but obviously there's a lot of room for improvement.
A large part of the problem is to do with non-specific symptoms of the cancer, that could easily be due to some other more minor cause. But processes have been set up to try and learn what happens when a cancer diagnosis is missed and why. It's called a Significant Event Audit and it is already embedded in UK general practice. It asks: what happened? Why did it happen? What has been learned? What has been changed?
This tool has been used to ask many GPs to do such an audit on the same topic, analyse the outcomes together and see if we can learn more about what is happening with GPs around the diagnosis of cancer. Such studies have shown that although many patients had presented with symptoms of their cancer, some hadn't and those that did almost always had multiple symptoms. It's a very difficult challenge for early detection of the disease when cancers appear as individual as the patient themselves.
Where there was a delayed diagnosis, there were a number of reasons. For example, some patients refused treatment or investigation, they were sometimes wrongly reassured by negative test results and patients sometimes had other diseases which made it difficult to detect the cancer.
The upshot of the session was that cancers can sometimes be very difficult to find. But measures have been put in place to try to address some of these issues. And as one of the presenters said: “GPs don't get up in the morning to miss a cancer diagnosis. We're all pulling in the same direction to improve things for patients, and hopefully we'll make good progress with patients and GPs working together."
Read our roundup of Monday's NCRI Conference talks, or join the conference debate on Twitter at #NCRI2014.
Dr Matthew Lam is Breakthrough Breast Cancer's Senior Research Officer, Dr Sarah Hazell is Breakthrough Breast Cancer's Research Insight Manager and Dr Emma Blamont is Breakthrough Breast Cancer's Senior Research Officer.