As part of Lung Cancer Awareness Month, we talk to Professor Angela Cox from the University of Sheffield, who is using our funding to develop a blood test for earlier diagnosis of lung cancer.
Ruby Osborn: Hello and welcome to the Weston Park Cancer Charity Podcast, sharing stories about our work, what we do and the people we support. From funding life-saving research to providing practical help and emotional support, it's our job to care in every sense for our patients and their families. Lung cancer is one of the most common cancers in the UK and the highest cause of cancer death. Here in Yorkshire, our lung cancer rates are above the national average. I’m Ruby and today I'm talking to one of our research grant holders, who’s working on a new way to diagnose lung cancer.
Angela Cox: I'm Professor Angela Cox and I work for the University of Sheffield. I'm a researcher, I’m a geneticist by training, and in recent years we've become interested in using genetics to develop a blood test for different forms of cancer. So we’re interested in lung cancer and it's one of the cancers that's often diagnosed when it's already at a very late stage of disease, and when that happens it's more difficult to treat and the outcomes for the patients are not so good. The symptoms aren't always terribly clear, patients often have a cough, they might have a cough for a long time and for whatever reason they might be reluctant to go to their doctors. I think it's a form of cancer that can creep up on the patient so it can already be quite advanced by the time the patient sees their doctor and gets referred.
Now we know that screening for some types of cancer, like breast cancer, bowel cancer, cervical cancer, screening for these helps with early detection of those cancers and it would be great if we had a method that we could use to screen for lung cancer so that we could detect it at an early stage when the cancer is more amenable to treatment. Currently patients with symptoms are referred for further testing such as CT scans and radiography to detect the presence of the cancer. So this involves travel to a specialist centre and use of expensive equipment and so on. A blood test could be carried out in the doctor's surgery, so it's a lot more convenient for the patient, and then the blood samples could be sent off to a central laboratory, so it's a much simpler test. It's not likely it would be sufficient to make a diagnosis but patients, where we detected these changes in the DNA in the blood, could then be referred for the more detailed testing.
Ruby: Who do you think would be tested using this? Would it be everybody or people in certain risk groups?
Angie: So most likely I think we would be testing people in risk groups. So this might be smokers or people with a strong family history of lung cancer, because these groups of people are probably at a higher risk of developing lung cancer so we'd focus the screening in those groups.
Ruby: What is the test that you're trying to develop?
Angie: We’re working on developing a blood test, and this blood test makes use of the fact that tumours shed some of their DNA into the blood stream, and we can make use of that because we can detect that DNA in the blood stream and we can also detect the genetic changes and mutations that are present in the tumour. So we’re developing methods to do that as part of our potential screening test.
There’s DNA circulating in our blood from all our cells in the body, because cells are continually dividing and dying, releasing their DNA into the blood stream, and this happens by various processes, and this happens a lot with tumours as well because tumour cells are proliferating but they're also dying, some of them, so it's that DNA that's released into the blood stream that we can detect. And we can distinguish the tumour DNA from the DNA that comes from your healthy cells because the tumour DNA contains lots of mutations and rearrangements, tumour DNA is really messed up, that's one of the characteristics of it, and what we're trying to do is assemble a lot of different types of genetic changes together in a in a score, if you like.
So what we're doing is we're combining genetic mutations in all different kinds of genes, and also another type of genetic change which is DNA copy number changes, so some regions of the genome become amplified in tumours and some regions get deleted, so our test is trying to combine all these different types of changes in the form of a score, which we can then use hopefully to distinguish people who have a tumour to people who don't have a tumour, so the higher the score, the more likely it is that you might be carrying a tumour. Healthy individuals you'd expect to have a very low score because there isn't any tumour DNA in their blood DNA, so that's that that's the basis of the test, if you like.
Ruby: Is there any danger from having tumour DNA in the blood, is that how cancer spreads around the body?
Angie: No it's not, not the DNA as such. The DNA in the blood is really just a by-product if you like of the tumour. Tumours spread around the body through the actual live cells of the tumour becoming mobile and detaching and making their way into the blood stream and spreading that way, it's not the DNA that's harmless, and like I said, we've all got low levels of DNA in our blood stream anyway from our healthy cells.
Ruby: So it's just an untapped source of information, really?
Angie: Absolutely, that's a really good way of putting it, it's a source of information that we can make use of. The current project is really a pilot study, so it's with a relatively small number of patients and control samples, and we use that study to design the next stage, if you like, which would be a larger study to give us an accurate estimate of the sensitivity of the test, so to allow us to work out how good the test is. And if the results of that second study were encouraging then the next step would be to have a prospective clinical trial, so it's quite a long road towards actually using the testing in patients.
Ruby: The blood samples that you're using in this pilot study, where are they from?
Angie: We asked patients and their relatives if they'd be willing to donate blood samples for this study, and in fact this study is part of a wider study called ReSoLuCent, which was set up by Professor Penella Woll, where she invited patients to donate a blood sample for future research. And the study doesn't benefit those patients directly so they are very kindly donating a blood sample for research in the hope that it might benefit future patients.
Most of the patients, when they come to the clinic about their lung cancer, they often come with their partner or perhaps a sibling comes along with them, for moral support, so we also invited those partners and siblings of patients to donate a blood sample as well, and then that forms the group of healthy control people. And then we can compare the performance of our test in the patients compared to that healthy control group. So we're really in debt to those patients and their relatives and partners.
Ruby Could a blood test be developed for any other types of cancer?
Angie: Absolutely. We had a project, which was also actually funded by Weston Park Cancer Charity, in melanoma, where we were looking to develop a similar type of blood test to detect relapse at an early stage of melanoma. We need to do a bit more work before it would get to the next stage of developing a clinical trial, so we need to do a larger study to confirm and ratify the results we got in the initial study. So that was one project that we did in our lab, but there's a lot of labs around the world using this sort of technology in a wide range of different types of cancer.
Yes, so in principle it's applicable to any type of cancer, and it could be used in a number of different settings so we're interested in the early detection of lung cancer for example, but like I said we, in melanoma, we looked at developing a test for early detection of relapse, it can be used to monitor patients after treatment, to detect minimal residual disease, responses to treatment and so on.
Ruby: Why is research important?
Angie: Research is absolutely vital, really, to generate the evidence that we need to make sure things are safe and effective to use in patients. So in terms of developing new treatments, you know, an excellent example is the development of PARP inhibitors which were developed by groups in Sheffield, Helen Bryant and Thomas Helleday, and those PARP inhibitors are now approved for use in certain types of breast cancer, ovarian and prostate cancer. That research which was published back in 2005 was the first step in developing those treatments. And similarly, our project is working on developing a test rather than a treatment, but we need to do the research to establish that the test is good enough and that it is effective, that it can detect cancers early and thus can provide benefits for patients. So that's why we need to do the research.
Ruby: What led you to being a researcher?
Angie: I did a degree in genetics in Cambridge and like many people I guess I didn't really know what I wanted to do, and I ended up working for a biotechnology company immediately after completing my undergraduate degree, and then I got the opportunity while I was working there to actually register for a PhD and do a PhD, and I guess it developed from there. Not too long after that came to work in Sheffield.
When I first came to Sheffield I was working on the genetics of autoimmune diseases, things like rheumatoid arthritis and type one diabetes, and in 2000 I moved over to cancer. For a number of years I was working on, and still am working on, identifying genetic predisposition factors for cancer, so what is it about our inheritance, our inherited DNA, that predisposes some people to cancer. And then I guess it was about five or ten years ago, the technology advanced sufficiently so that we were able to analyse these very small amounts of DNA from the tumour in the blood stream, so we turned our attention to looking at that and that's brought us to where we are today with this current project.
Ruby: What makes Sheffield a good place to do research?
Angie: Sheffield is a fantastic place to do research and I would say the main reason for that is the willingness to collaborate of people in Sheffield. So those relationships between clinical colleagues and the scientific laboratory-based work is absolutely vital so that, you know, we can make sure that the research we're doing is the right research that's going to help patients in the future.
Ruby: Thank you for listening to this episode of the Weston Park Cancer Charity podcast. That was Professor Angela Cox from the University of Sheffield. If you want to help us continue to enable research like this, visit our website, westernpark.org.uk, or give us a call on 0114 553 3330.
Dean Andrews: Cancer changes everything, but so can we.