Cancer research at the Leeds Institute of Molecular Medicine

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Published: 11 Jan 2011
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Prof Pamela Rabbitts - Leeds Institute of Molecular Medicine, UK
Prof Pamela Rabbitts talks about the Leeds Institute of Molecular Medicine and the work she has been doing on lung cancer and head and neck cancer. These two cancers show a number of similarities but head and neck cancer is much more accessible for research, especially in the precancer stage. Prof Rabbitts discusses her particular interest in cancer genomics, talks about the difficulties collecting tissue samples from thoracotomies and explains the potential role of HPV in the stratification of head and neck cancer patients.

NCRI Cancer Conference 2010, 7 November 2010, Liverpool

Professor Pamela Rabbitts – Leeds Institute of Molecular Medicine, UK

Cancer research at the Leeds Institute of Molecular Medicine

About four or five years ago the Leeds Institute for Molecular Medicine was opened, taking advantage of the fact that there was really quite a lot of interest in cancer research in Leeds, particularly because CRUK had been there for a number of years, and the sort of close proximity of the research and the hospital, St James NHS Trust Hospital which is a huge hospital with a really big catchment area, and we wanted to take advantage of that, and have the clinicians and the scientists, not just working together but working together on the same campus. And it actually does matter, that; clinicians are busy, you need to be able to catch them ten minutes here, ten minutes there, can’t be meetings all the time, and that is what we found really, really beneficial.

Leeds has a reputation, well deserved, over the last 10, 15, 20 years in a number of cancer types and also some technologies. Where is the newest that you’d focus on?

It focuses across a number of tumour types and I have brought an interest in lung cancer where there wasn’t a research interest in lung cancer before, because of work that I had done previously. We wanted to bring my approach to working on very early lung cancer to Leeds and the idea there is that if you study the disease early you are able to treat it early and there your chances of cure are much higher. But while I was there I was also introduced to the head and neck team. Now head and neck is quite a rare disease, it’s sixth in the world – it’s not that rare, but it’s fairly rare in the UK but it has an awful lot in common with lung cancer and it’s much more accessible, and particularly if you work on what I call pre-cancer. So those are those stages where the abnormalities are visible in the mouth, not visible in the lung, but are not actually invasive. So if you could catch cancer at that stage you would catch it before it became malignant and before it spread, and that’s the real attraction to me. It’s an excellent sort of therapeutic target.

My interest has always been in genomics, and there are obviously lots of ways you can look at cancer and pre-cancer, but I like to study alterations in the genome and that’s because I’m really convinced that alterations in the genome are what drive cancer forward. We know that really from very early work where we were able to identify mutations in genes and actually show that the mutation was causing a tumour in cell-free systems. Of course viruses were carrying the same mutations, but we look more generally beyond genes now, just as we were hearing actually in the talk, that you should look at the whole genome, the pattern of the genome. I have a new post doc who is taking an interest in what’s called non-coding RNA, so this is the large parts of the genome that are transcribed; they are copied, they are doing something but they are not making proteins, and we are very interested in what their involvement is in cancer. The way we work is always asking what’s the difference; if you get pre-cancer and cancer and compare them, what’s the difference? And the way that I do this, and it’s hard I can tell you, is to work on patient material. I have worked on mouse models, I do use cell lines, but I am absolutely devoted to the idea that we should get samples from patients and work with those.

How many thoracotomies for lung cancer are done in Leeds Institute in a year?

Well you know I can tell you the answer to that, because we have just written a paper and there were over 300 resections for lung cancer. And what was interesting, and dismaying, when we wrote our paper was we were quite professional about collecting them; we have a tissue collector whose job it is full time, and yet we found that we were only actually able to retrieve about 15% of them.

One five?

Yes, and this isn’t because patients won’t consent; it’s all the difficulties around consent, when it’s done, how we manage it. It’s sometimes the list is changed, sometimes the patients go to another hospital to meet NHS targets and we don’t get the tumour. So it has been a quite interesting study to show actually that although there’s a lot of lung cancer in Leeds, we are not very effective at collecting it yet, and we need to get much more professional about that.

Are you going to set up a spiral CT program now that the American trials have been halved, because spiral CT saves lives?

It wouldn’t be my job to do it, I’m a molecular biologist, but I’ll certainly be encouraging it.

Because you’ll get early material then.

Yes, we will, we will get early material, yeah.

Interventions based on what differences you pick up between pre-malignant and malignant?

There aren’t really any yet because the data are not really there to generate those, but what is interesting in our work, and this is the way things happen – just a little side line really, is that I started to work on HPV in head and neck cancer. This hadn’t been an interest of mine before but I was intrigued by the idea that HPV could stratify patients and the fact that the expectation is we will actually patients differently if they’re positive for HPV or if they don’t have HPV. And that means that the detection of HPV is going to be absolutely crucial, and we are discussing various ways of doing it at the moment, what’s the best way, what’s the combination of ways, and what we’ve done in our lab is we’ve shown that you can use next generation sequencing to detect HPV. A rather nice thing about doing that is when you detect the HPV at the flick of a switch, and it’s not me who flicks it, but at the flick of a switch you can ask the question, which HPV sub type is it? So you can look, there’s over a hundred actually, and in seconds you will, because the answer is almost always HPV16, but that’s something you can do with sequencing that’s a long job. The other thing is it gives you actual viral load so if you look for the detection of HPV16 by looking for a surrogate such as P16, too many 16s, that’s very effective but you don’t get viral load from immunohistochemistry. So we are rather excited about this way of detecting HPV. We don’t say it’s the be all and end all but it will certainly add to the methods doing it, and the great thing about it as well is when you do this methodology you actually get a karyotype, so we are looking at copy number essentially. So you get the copy number across the genome, which genes are lost, which are gained, and you also get this HPV digital readout. So that’s happened just since I’ve been in Leeds.

The epidemiology, as I understand, is quite different between the HPV positive head and neck cancers and the HPV negative ones.

That’s so.

They are asking the question, so which treatments are you going to give to one and to the other, and is this going to be important? I agree with you, I think the evidence is that it’s already important.

Exactly so, and the means of detection is going to be crucial. And it might turn out , as things often do in clinical medicine, as you know only too well, to be rather more complicated than we think, and we might get patients who have an HPV phenotype, they are HPV positive, but nonetheless their tumour has actually been driven by tobacco exposure and they are going to need a different treatment. So it’s a complicated area but we think we are making a small contribution.

Pamela, thank you very much. We appreciate your speaking with us.

It’s a pleasure.