Pioneering breast cancer research

Interviewer: Lucy Vernall  (Interviewer, Ideas Lab)
Guest:  Dr Clare Davies
Recorded: 17/12/2012
Broadcast: 19/12/2012

Intro VO: Welcome to the Ideas Lab Predictor Podcast from the University of Birmingham. In each edition we hear from an expert in a different field, who gives us insider information on key trends, upcoming events, and what they think the near future holds.

Lucy: Today I’m in Cancer Sciences at the University of Birmingham with Dr Clare Davies. Welcome Clare. 

Clare: Hello.

Lucy: And you’re one of the new Birmingham Fellows, a very special Fellow. Tell us about the Fellowship Scheme.

Clare: The Birmingham Fellowship Scheme is an amazing opportunity for people in my situation whereby I’ve done my academic training and my post-doctoral studies and I have my own ideas and I want to really look into them and to make what I feel is a difference in cancer research and the Birmingham Fellowship basically provides me with support to enable me to do this and to set up my own research group to answer the important questions. 

Lucy: And you’re actually an alumna.

Clare: I am, indeed.  I did my undergrad degree here, I did the BMedSci programme and I did my PhD in cancer sciences so after moving to London for five years and then Manchester for two years, I’ve come back. So it’s a full circle for me. 

Lucy: Well welcome back. We’re very glad to have you.  You are specialising in breast cancer research.

Clare: Yes I am. 

Lucy: Tell us a bit more about what you’re going to be doing over the period of your Fellowship.

Clare: So I’m interested in a family of enzymes called ‘Protein Arginine-Methyltransferase’ or PRMTs and these enzymes are very interesting because they can modify the behaviour of a protein and either promote protein complex formation or prevent proteins from interacting together. 

Lucy: So are these found in every cell in the body or just in specific - 

Clare: They are indeed found in every cell in the body but what we and other people, other researchers, have found is that PRMTs are up-regulated so their protein expression is increased in certain tumour types and specifically in breast cancer.  

Lucy: So there are a lot more of them around. 

Clare: Yes, there is indeed, yes. 

Lucy:  So there are more PRMTs when you’ve got breast cancer, in the breast cancer cells or in all cells in the body?

Clare:  So we know that their expression is elevated in the breast cancer tissue compared to the normal tissue that surrounds the cancer, so this implies that PRMTs could be causative in promoting tumour regenesis. 

Lucy: So they’re actually making tumours happen?

Clare:  Exactly, exactly. But whilst this is a hypothesis, at the moment we’re still not 100% sure that this is the case so what my research will be doing is to look at the role of PRMTs in breast cancer formation and we want to understand the molecular mechanisms by which PRMTs promote tumour formation. 

Lucy: So it’s ‘are these PRMTs there because there’s cancer, or is cancer there because of the PRMTs?’.

Clare:  Exactly, exactly.  So is it cause or consequence, basically.

Lucy: So how might this down the line make a difference to somebody who has breast cancer?

Clare: So, because these proteins are enzymes that means we can target them for therapeutic intervention. So by that I mean we can design drugs which can specifically bind to these proteins and inhibit their activity. So if PRMTs are up-regulated in breast cancer and causing breast cancer to progress, if we inhibit these enzymes we might slow down or even prevent breast cancer from forming. 

Lucy: So would that mean there’s a whole new way to go about treating breast cancer?

Claire:  I think with breast cancer what we should remember is that there are current therapeutic strategies available at the moment for the different subtypes of breast cancer, so if you have ER positive  breast cancer you’re often treated with - 

Lucy: ER positive means?

Clare: So ER means oestrogen receptor positive breast cancer and women with this subtype of breast cancer are often prescribed Tamoxifen for treatment. Now whilst tumours will regress, quite often they can reoccur, what we call relapse, and this is because the tumour cells have acquired drug resistance. 

Lucy: So you can actually get drug resistance to cancer treatment, because I thought drug resistance was something that just happened with antibiotics. 

Clare: Yes, indeed you can and this is because cancer cells are incredibly clever and they can change the way they adapt to various environments. So by being exposed to a compound for a long period of time, they can change their genetic make-up which enables them to become resistant to that compound and as such that compound doesn’t kill the cancer cell anymore. 

Lucy: So this is why we need another way to go. 

Clare: Exactly.  If we, we always need to look at alternative ways in which we can target breast cancer cells for therapeutic intervention and proteins such as PRMTs are one avenue that could potentially be incredibly fruitful and be a potential drug target. 

Lucy: So you’re right at the start of this aren’t you?

Clare:  I am indeed, yes!

Lucy: Literally with a few cells in a petri dish, is that where things are at?

Clare: This is it, yes!  At the moment, yes. 

Lucy: And where do they come from and literally how does the research work?

Clare: So the research works twofold mainly.  Firstly we do a lot of our work using human breast cancer cell lines that we can grow in our labs, but by using these cell lines we can genetically manipulate the cells to investigate certain proteins – so in my case PRMTs – to see how they contribute to various cancer phenotypes.  So a phenotype is a cell behaviour such as growth or their ability to be killed by known chemotherapeutic agents. 

Lucy: And so presumably at some point you move from the petri dish to patients?

Claire: We do indeed. One avenue of research we are looking at is that breast cancer is an incredibly complex and heterogeneous disease and by that I mean that there are different molecular subtypes of breast cancer, so being told you have breast cancer doesn’t mean that you have the same type of breast cancer as another breast cancer patient. 

Lucy: So there are a load of different kinds. 

Clare:  Exactly. So what I’m interested in is really looking in close detail at what types of human breast cancer over express the PRMT proteins. So not only would this be able for us to say OK, once we develop an inhibitor we should target subtype X, it could also be useful as a biomarker. So by that I mean taking a human biopsy sample and looking for proteins that are known to be up-regulated and indicative of a disease state. 

Lucy:  So the sample that you would get from a patient, the presence or absence of PRMTs might tell you a little bit more about exactly what type of cancer they have?

Clare: Yes, yes and actually ultimately how we could treat it, yes.  Yeah, more sort of the clinical prognosis for that patient.  So maybe by screening a large number of human breast cancer we’d be able to identify which subtype or what type of disease state PRMT expression levels are elevated and perhaps then maybe we can then correlate this to which treatment patients should be receiving. 

Lucy: So by testing for PRMTs in different samples it will just give us a lot more information.

Clare: Absolutely.  This is work that’s not really been done. We’re only sort of touching the tip of the iceberg of the role of these proteins in breast cancer so we need to go from the fundamental cell biology, all the way up through to looking at them in human biopsies.

Lucy: And of course Birmingham is a great place to do that. 

Clare: It is indeed.  We have, well I’ve been told, Europe’s largest hospital on our doorstep, the Queen Elizabeth, and it’s amazing. There’s a wonderful facility whereby we can obtain ethically approved human biopsy samples which makes this research a real possibility that it will happen. 

Lucy: So your current position is for five years. 

Clare:  It is indeed. 

Lucy: Which is quite a short amount of time with the type of science we’re talking about. 

Clare: Yes, in life sciences five years is not very long, it will whizz by!

Lucy: But a really, really exciting area with massive potential. 

Clare: Absolutely.   I mean it’s been relatively overlooked in the field and I think it’s an incredibly exciting and novel research area and I think we’ll make a real difference to the lives of breast cancer patients in the future.  I think with all research it will take a long time but we have to start somewhere at understanding the role of these proteins in tumour biology.

Lucy: And there’s a lovely ending to this little chat which is that your Fellowship has been funded by an alumnus, a previous Birmingham person, who’s actually given the money to the university to allow your research to go ahead.  You’ve actually met him haven’t you?

Clare: I did indeed. 

Lucy: So you’re a Murphy Research Fellow. 

Clare:  I am indeed. I met the gentleman in April this year, we had a lovely chat for a couple of hours about my research and really how his money will be spent and he seemed very excited about the work and it’s just very reassuring to have support from somebody who’s been personally affected by breast cancer.  I feel very very privileged to have his support. 

Lucy: So we’re very grateful to Neil Murphy for allowing you to be with us, Clare. 

Clare: Thank you. 

Lucy: Thanks very much for sharing your research with you and have a lovely Christmas. 

Clare: Yeah, thank you. You too. 

Outro VO: This podcast and others in the series are available on the Ideas Lab website: On the website, you can find out how to e-mail us with comments, questions or suggestions for future topics for the podcast. There's also information on the free support Ideas Lab has to offer to TV and radio producers, new media producers and journalists. The interviewer for the Ideas Lab Predictor podcast was Lucy Vernall and the producer was Sam Walter.