The Pill and cancer risk, sensitising tumours, and physicists fight cancer

Cancer Research UK
How the Pill affects cancer risk, making tumours more sensitive to treatment, and fighting cancer with physics.


Kat: This is the Cancer Research UK podcast for August 2014. This month we discuss the Pill and breast cancer risk, discover how to make tumours more sensitive to treatment, and hear how physicists are fighting cancer. Plus our heroes and zeros.

Hello and welcome, I’m Dr Kat Arney. And joining me for a chat about this month’s news is senior science information officer Dr Emma Smith. 

The first story I wanted to talk about was the rather alarming headlines that we’ve seen warning women that taking the oral contraceptive Pill is linked to breast cancer. What do we know about this?

Emma: We already knew that taking the Pill can slightly raise the risk of breast cancer, but at the same time there are advantages to taking the Pill, because it also reduces the risk of womb and ovarian cancers. So a big group in America have done a really large study on more than a thousand women and come up with some interesting results.

Kat: Tell me about this new study – what did they look at?

Emma: They were using the women’s insurance records, which is good because that keeps a really accurate record of what Pill they were taking. And what they did was they looked at women who went on to develop breast cancer and compared the number of women who had taken the Pill in the previous year and compared them to the number that hadn’t. And they were also looking at what different types of Pill the women had taken – so the exact formulation of the Pill, if you like.

Kat: What were the outcomes? What did they find?

Emma: What they found is that despite the media coverage, there wasn’t a strong increased risk associated with different types of Pill – all the different types of Pill had roughly the same kind of effect. 

Kat: What kind of risk are we talking about here? Is this a major risk? Should we be concerned?

Emma: We’re talking about a 50 per cent increased risk.   

Kat: That sounds big!

Emma: But you have to remember that these are very small numbers of women we’re talking about. The kind of women taking the Pill are young, fertile, and the risk of them getting breast cancer in the first place is actually very small. We’re talking about the same kind of risk as drinking a glass of wine every day.

Kat: Are there any problems with this study? We hear a lot about studies that come out saying “This is a risk, this is not a risk” and when you actually look at the details there are some devils in those details.

Emma: It was quite a big study, and the good point was that it was using insurance records so the information was accurate. But it didn’t have full information about the women’s family history, or whether they’d been for screening or not, and that can make a difference. But the most important things is that they didn’t have information on if the women had taken the Pill in years before the year prior to diagnosis, and this can make a difference because taking the Pill can increase the risk of breast cancer for up to a decade. So by not having that information we don’t know if women were taking the Pill say five years prior to them getting diagnosed with breast cancer.

Kat: Or of they’d just started, I guess.

Emma: Or if they’d just started, or just stopped.  That does make a difference.

Kat: To give us a little bit more perspective on this we spoke to Sarah Williams, our senior health information officer. This is what she had to say.

Sarah: I think the most important thing for women to remember when they’re looking at this story is that while we do already know that the Pill does increase the risk of breast cancer slightly, and that actually goes away within ten years of you stopping taking the Pill, the Pill has effects on other types of cancer too. So overall, it slightly increases the risk of breast and cervical cancer, and that goes away over time, but it has a lasting effect of protecting you against ovarian and womb cancers. So on balance, the Pill actually prevents more cases of cancer than it causes.

Kat: That was Sarah Williams there.  So what overall should be our advice to women who are maybe worried about this?

Emma: You can always speak to your GP if you have concerns. But we don’t advise women to suddenly throw their Pill in the bin. As I said, it can have good benefits as well, like protecting you from womb and ovarian cancers. So when it comes to cancer the Pill has advantages and disadvantages, and we think women just need clear information about the risks, how much it increases the risk, and if they have any concerns go and talk to your GP.

Kat: And we do have an in-depth post about all of that on our Science Blog.  Now the next story I noticed was a really lovely story about something called APC, or the Anaphase Promoting Complex, which sounds like something maybe out of Star Wars. But this was some research from our scientists at The Institute of Cancer Research, and another team at the MRC Laboratory of Molecular Biology in Cambridge. And what they’ve done is figured out the three-dimensional; structure of this molecule called APC. Now this is an incredible molecular machine – it’s made up of more than 20 different subunits - bits that all come together to make it work. I like to think of it as a molecular Swiss Army knife. It’s really important in cancer.

Emma: What does this molecule do?

Kat: So it does a lot of different things. If you imagine is as a Swiss Army knife it’s got things like scissors, the thing for getting stones out of horses/ hooves, a corkscrew… It does a lot of different jobs in helping cells to divide. And this is not just healthy cells, which obviously need to divide to repair damage, to help us grow and all that kind of thing, but also cancer cells. Because cancer is just cells growing out of control. And what the researchers have done is used a really clever technique called X-ray crystallography, which is like taking X-rays of molecules, to work out the exact three-dimensional shapes of all twenty components of the APC, to put them all together and figure out how they work.

Emma: What’s important about knowing the structure of APC? What potential does it have?

Kat: It’s really important to understand these molecular machines because they tell us a lot about how they’re working, and then they tell us a lot about how they’ve gone wrong. So for example if you have your Swiss Army knife and it’s not cutting things, then you know that maybe the scissors are wrong and you want to work out how they’ve gone wrong. Is there a bit missing, or have they gone blunt? And in the same way this leads us to potential new therapies for cancer, because if we can understand how things are working, how they’re working when things aren’t going right, perhaps we could develop drugs or design drugs that would block exactly the right bit to target cancer.

Emma: So what kind of techniques did they use? Was it biology, or did it incorporate lots of numbers? It sounds very complicated.

Kat: This is something called crystallography, which is – like I said – shining X-rays through molecules. And, as we’ll hear later in the programme, there’s a really important role for mathematicians and physicists to work together with biologists to answer these complex biological questions. So it’s a really nice example of bringing together physicists, mathematicians, to try and solve these knotty problems.

And so finally the last story I wanted to talk about was a really interesting story I noticed from our researcher Claudia Wellbrock and her team at the University of Manchester. This is about skin cancer cells ‘piggy-backing’ onto each other. Emma, tell me a bit more about this.

Emma: The really intriguing thing was that Claudia Wellbrock actually used zebrafish as a model to look at skin cancer cells. Now as they’re developing from a little embryo, zebrafish are completely transparent, which is great as it means you can actually see the cells moving and where they’re going. So using this model she was able to study in detail how skin cancer cells were spreading, and she came up with some really interesting ideas. What she showed was that these melanoma cells can be two different types – some of them grow really quickly, and other ones are able to escape from the initial site of the tumour and spread really quickly. But they either do one or the other. Now the interesting thing is the ones that can escape – the ones that can invade out of the tissue – they’re actually giving the fast-growing cells a lift, a piggy-back if you like. So the ones that were fast-growing and couldn’t escape were jumping on the ones that were good at escaping, moving to another part and then growing rapidly again into a tumour. So it’s really exciting.

Kat: This seems really interesting because we have the idea maybe that cancers spread by first invading and then growing rapidly, but this suggests there are different types of cells in a tumour, and they’re co-operating to spread. This is quite an interesting finding, isn’t it?

Emma: Yes, almost like they’re specialising and having different roles and helping each other. The good news is that if we find out how they’re helping each other and co-operating we can possibly start to look at developing approaches to interfere with this co-operation, stop them helping each other.

Kat: I guess that’s really important because melanoma is a disease that’s very highly treatable if you detect it early – surgery is a really effective treatment. But the problem is one its spread it does spread very aggressively and then becomes very difficult to treat. Do you think that there is hope that understanding more could lead to future therapies for cancer that has spread?

Emma: Absolutely. As you said, it’s very easy to treat melanoma to treat if caught in the early stages, but when it has spread it becomes a lot more difficult to treat. And if you can think of ways to stop the cells spreading in the first place, or stop them spreading once they have started to metastasise, we have a real golden opportunity to make treatments better for people with advanced melanoma and help more people survive it.

Kat: And if you’re interested in that there are some fantastic images and a video on our Science Blog. Thanks very much Emma.

Also this month, our scientists at the Barts Cancer Institute made an important discovery about how to make tumours more sensitive to the effects of anti-cancer drugs. Our reporter Alan Worsley spoke to Professor Kairbaan Hodivala-Dilke, who led the work, to find out more.

Kairbaan: One of the ways that cancer grows and spread is because it gets a lot of oxygen and nutrients from the blood supply. And that blood supply is delivered to the cancer by blood vessels. So we’ve been working on how to change the blood vessels, or even kill the blood vessels, to try and kill the cancer. But that’s got a lot of problems associated with it. So the paper that we’ve just published is a slightly different angle, because what we’ve done here is instead of trying to get rid of the blood vessels, we’ve just genetically manipulated them a little bit. And it turns out that cancers that would otherwise be resistant to certain types of chemotherapy can now become sensitive to those chemotherapies because of the way we’ve changed the blood vessels.

Alan: In essence, you started with the idea of angiogenesis, the growth of blood vessels and trying to starve it out, and that’s had some problems. But instead you’ve worked out just tweaking it as opposed to getting rid of it.

Kairbaan: Yes, exactly. I think the important part of tweaking the blood vessels is that being able to deliver drugs that just tweak the blood vessels is probably easier than trying to deliver things that are really going to kill the blood vessels, so that’s probably got an advantage in the future. We haven’t done anything on that yet, but I can see that in the future. And then also because chemo-resistance is such a big problem clinically – people come in, they present with a tumour and they’re given a drug, and the drug works for a while and then after a while the cancer comes back again. And it comes back because they’ve become resistant to the therapy. So this is a way of instead of trying to attack the tumour just by itself, it’s a way of suing our blood vessels to help us attack the cancer better.

Alan: And how did that extra step happen? What got you into thinking “What if we combine it with chemotherapy?”

Kairbaan: Bernardo Tavora, who’s the lead on this work, read a paper from a lab in Boston led by Michael Hemann, and he had just discovered that blood vessels aren’t just pipes that deliver oxygen and nutrients to the tumour, but actually the cells in the blood vessels can ‘talk’ to the tumour cells. At that time nobody knew how that talking was controlled. So we thought well, we know that FAK is involved in cross-talk and signalling, so let’s see if in our experiments we can show that it can enhance chemosensitisation if we get rid of FAK in the blood vessels, and that’s where the really exciting data came through. 

Alan: And when you say you’re tweaking the blood vessels, this is using this molecule called FAK, for Focal Adhesion Kinase. What exactly is FAK?

Kairbaan: So FAK is a small molecule that’s found inside cells, and it’s called a signalling molecule. It’s a bit like a telephone wire, it takes signals from the nucleus out to the surface of the cell, and it takes signals from the outside of the cell into the nucleus, and in that way it’s a way of being able to help the cell respond to its environment and respond to stresses. So it’s an important molecule. It’s in the middle of a lot of signalling pathways. 

Alan: So FAK is involved whenever the environment feels some sort of stress, exactly as you’d expect from chemotherapy or radiation in response to that. So what does it say to the environment?

Kairbaan: In the blood vessel cells, what it is doing is that if you take away FAK, we’ve realised that actually the cell doesn’t respond in the same way to the DNA-damaging agents, the chemotherapeutic agents. And what happens is it doesn’t make a whole soup of what we call cytokines – these are different molecules that are thrown out of the cell. So if we think about a normal situation first – normal blood vessels, when they’re damaged with DNA-damaging therapy, they will make a cocktail of 40 or 50 different sorts of cytokines. And these actually, what we found, are protecting the tumour cells from the chemotherapy. So they’re throwing this invisibility blanket over the tumour cells, right? But now if we just take away FAK from the blood vessels, they can’t do that any more, so now these tumour cells are left naked, and now the chemotherapy works better.

Alan: So in a sense this molecule, FAK, that’s in the blood vessels, that’s normally trying to do what it should do to repair damage from an injury – it just doesn’t realise that we don’t want that cancer to be repaired, we’re trying to attack it but it’s creating this barrier. And just by removing FAK it just improves the ability of chemotherapy to get there.

Kairbaan: FAK is an important molecule – it’s actually found in lots of different cell types including cancer cells. But actually inhibitors of FAK are already being made to be tested clinically to treat cancer. But most of the focus on that is in the tumour cells, not in the blood vessels. So this is where this particular piece of work is a step forward, because it’s telling us that if we only focus on the tumour cells there’s still a lot to learn by actually manipulating the surrounding tissue, and especially the blood vessels. 

Alan: What do you think this says about how we go about researching cancer, in the sense that although this is in the cancer, it’s really the FAK in the blood vessels that’s giving this result?

Kairbaan: Maybe 20 years ago people used to work on their little pet subject, and I think it’s become more and more evident – and it’s just common sense actually – that we need to integrate better. I quite often say to people if I just give you sugar you’ll taste the sugar, you’ll taste the sugar. And if I just give you flour you’ll taste the flour. But if you put them all together to make a cake, that’s the flavour you’re after. And that’s what cancer is. We need to think about the whole cake in one go, I think.

Kat: That was Kairbaan Hodivala-Dilke from the Barts Cancer Institute, and there’s more about her work on our Science Blog.

Now, when you think about cancer researchers, you probably think about biologists working in a lab, or doctors treating patients. But there’s a growing role for physicists and mathematicians in helping us to beat cancer too.  I chatted over Skype to physicist Dr David Robert Grimes from Oxford University about his research, aiming to understand more about how differing oxygen levels affect radiotherapy – and discovered that he’s also been up to a bit of fun in his spare time too.

David: In tumours, oxygen distribution plays a really vital role. If tumours are well-oxygenated they tend to respond better to radiotherapy, and indeed chemotherapy. Now with modern technologies we’re able to image to the millimetre, usually, where oxygen might be. But the real problem for us is that oxygen varies over a micron scale, so a thousand times smaller than we can actually see. And for that reason mathematical modelling becomes vital to try to understand what’s happening at those levels.

Kat: So you can’t actually see it, but you can use maths to infer where these different oxygen levels might be?

David: Absolutely, that’s what we’re hoping to do. Because if we can do that we could then say, “Alright, this area here is low in oxygen – let’s selectively boost the dose to this area”. This is a concept known as dose-painting. But if we’re going to be able to dose-paint, we have to have a pretty good idea of where the oxygen is and what regions are well oxygenated or not. So a lot of my research would be based around understanding and quantifying oxygen distribution inside tumours, and there’s a lot of physics in that as well. People always ask me, “What’s a physicist doing in cancer research?” There’s a lot of us doing things just like this!

Kat: So how do you go about trying to work out what the distribution of oxygen is like on this microscopic scale in a tumour? 

David: Well the first thing you look at is to establish a framework to work out what’s happening. Physicists are very reductive creatures, we try to bring things down to the most basic thing that’s happening. And the most basic thing that’s happening is oxygen is diffusing through the tissue, but as wit’s diffusing through the tissue it’s being consumed by hungry cells that use oxygen as part of their metabolism. So it goes a certain distance and its quantity is reduced, reduced, reduced and eventually it can’t go any further. So we model that usually as a series of reaction diffusion equations. And there’s a lot of mathematical trickery there, but the basic idea is that oxygen is trying to get through somewhere but it’s being consumed and stripped away as it goes down. But what makes it a bit more complicated is that, for instance, we use a thing called tumour spheroids, which are very basic spheres of cancer. And we can very accurately estimate them and see how the oxygen went through them. That’s easy to validate and we’ve done some work on that. But when you’re looking at real in situ tumours, you have a problem with their chaotic vasculature – the oxygen supply of a tumour comes mainly from vessels that spring up and go through them. But tumours encourage chaotic vasculature. They send out signals saying “Build more vessels here! Build vessels here!” and the oxygen distribution can be really complicated inside a real tumour. So we’re doing work on trying to model that, and it becomes significantly more difficult.

Kat: There’s been a lot of advances in radiotherapy over recent years – for example we have image-guided radiotherapy, we have all kinds of ways of making it much more targeted and accurate. But people still have this idea that it’s a very old-fashioned therapy. Do you think that the kind of work you’re doing to make it more accurate and effective is going to be an important part of the future of cancer treatment?

David: I hope so it’s. It’s interesting that you mention that, because historically in some regards it is a very old idea of therapy. What’s happened over the years is the refinement. We knew years ago that if you fire radiation at a tumour, you’ll kill tumour cells. And that was great. But it’s become so much more elegant than just that. I mean, now we shape the beams. Some of your listeners have probably seen the very advanced gantries that pivot around, and what they’re doing – and there’s incredibly mathematics behind this – is they’re working out the maximum angle that they can hit the tumour with the maximum dose and minimise it to everything else. So it really is quite sophisticated, despite the actual mechanism being fairly blunt.

Kat: As you mentioned it’s unusual that a physicist should be involved in cancer research, but obviously we need physicists and chemists and mathematicians to make progress in beating this disease. What kinds of things are people like you doing to help us beat cancer?

David: As I mentioned earlier, I think physicists work in a reductive mindset. So what we do is try to simplify the picture down and work in small incremental steps what we can do to build onto it. A lot of physicists who work in cancer research actually specifically work on beam shaping and radiotherapy. They work in making dose prescriptions and dose plans, working out how to maximise dose to the areas you need it and minimise it to the areas you don’t. And then there’s people like me who do modelling of what’s happening inside the tumour, and there’s other people doing modelling of how the patient might respond. All of these different elements do come together in a kind of symphonic way to improve treatments for patients in the long run. But it is an interesting picture, as you point out, that we don’t traditionally associate mathematicians and physicists as having a big role in cancer therapy yet they really do. It’s just more behind-the-scenes than people might be aware of.

Kat: And as a physicist I understand you have a slightly interesting sideline, and have just published a paper looking at the physics of playing the guitar in your spare time. Tell me about this.

David: Yeah, that’s a little bit interesting. I’m a keen musician as well, and as I have mentioned physicists being very reductive, I’ve always been curious about when I use certain techniques on the guitar – which I do instinctively like any guitarist – I want to know what mechanically is happening. What am I doing to these strings that is making the pitch change this way? And it turns out that you can make it into quite a simple analysis, and you can work out that pushing a string up when you’re physically manipulating the length of it and the tension and the angle to which you’re bending it – you can work out all these factors and work out what pitch that would produce. That’s of a sideline of mine doing little things like that. 

Kat: Dr David Robert Grimes from Oxford University – and you can find out more about his hobby project on the physics of lead guitar playing by following the link in the SoundCloud player.

Now it’s time for our heroes and zeros. Our hero this month is Professor Andy Pearson, one of our amazing children’s cancer researchers at the Royal Marsden Hospital in London. He’s leading our groundbreaking BEACON trial, aiming to find the best way to treat children with neuroblastoma that has come back after treatment. When Andy began his career as a medical student in the 1970s, fewer than two in every 10 children survived neuroblastoma. Thanks to research, that figure now sits at six in 10, and we hope his new trial will boost it even further. You can read more about his story and the trial on our Science Blog. 

And finally, our zero this month is DIY sunscreen. Some newspapers have been reporting that people are turning to home-made alternatives to sunscreen. The problem is that it’s impossible to know how well they protect against cancer-causing UV radiation, if at all, and would strongly advise against whipping up a quick batch in the kitchen.  Our advice is that sunscreen should be your last line of defence against the sun – it’s better to seek shade during the hottest parts of the day and protect yourself with clothes, hat and sunglasses. But if you need to use sunscreen for the bits you can’t cover, go for one off the shelf with a high UVA star rating and at least SPF15. It doesn’t have to be expensive – own-brand makes from high street stores are just as good. 

That’s all for this month, we’ll see you again next month for a look at all the latest cancer news.

We’d also like to answer your questions in our podcast, so please email them to, post on our Facebook page, or tweet us – that’s @CR_UK. And if you’re listening to this on Soundcloud, please leave us a comment with your feedback. Thanks very much and bye for now.