Can you teach an old drug new tricks? Thanks to a project grant from our Population Research Committee, Dr Des Powe hopes to find out.
Cancer cells have a tendency to spread (or metastasise) to other sites in the body, forming secondary tumours. Once this has happened, the disease can be difficult to treat. In the next in our series of Expert Opinion interviews, Dr Powe discusses his plans to find out whether a common drug could stop cancer in its tracks.
Cancer Research UK: Why are you so interested in breast cancer spread?
Des Powe: Around a third of breast cancer patients develop metastasis but those patients account for 90 per cent of breast cancer-associated deaths. So, if you can stop the cancer spreading in the first place, you could save the majority of those patients from dying and improve their quality of life in the process. And really that’s what my study is about.
Cancer Research UK: Could you tell us about the background underpinning your work?
Des Powe: Our approach is based on how cancer cells migrate. In the early 1990s, laboratory studies showed that the stress hormone norepinephrine (also known as noradrenaline) could make cancer cells migrate or move. Norepinephrine sticks to a molecule on the cell surface called the ‘adrenergic receptor’ and if you block this receptor, you stop cell migration.
Fortunately, drugs that block the noradrenergic receptor are already on the market – they are called beta-blockers, and they’re commonly used to treat cardiovascular disease and anxiety. So the question that we set out to address was whether beta-blockers stop metastasis in breast cancer.
Cancer Research UK: And where are you now with your research?
Des Powe: In 2009, we performed an initial population study of around 500 women who had had breast cancer. We found that women who had already been treated with beta-blockers prior to their breast cancer diagnosis were 51 per cent less likely to develop metastasis. And they had a 71 per cent decreased risk of cancer-associated death, which was very encouraging.
Two other studies that were performed after ours supported our findings. Now we need a more powerful study using a much larger population size and that’s what I’ll be doing with Cancer Research UK.
Cancer Research UK: Could you tell us a bit more about the larger study?
Des Powe: The idea is that if beta-blockers can stop the formation of secondary cancers, the patient should do better. We’ll go through patient records for around 30,000 breast cancer patients looking at tumour recurrence and survival to see whether patients previously treated with beta-blockers live longer. We’d also like to understand the role of dosage and duration of treatment with beta-blockers and find out whether certain types of beta-blocker are more effective than others.
If these results confirm our previous findings, then there will be a very strong case for commencing clinical trials to test whether giving beta-blockers to women diagnosed with breast cancer can improve survival.
Cancer Research UK: How long do you expect this work to take?
Des Powe: We’re pushing to try and get it done in one year. I believe it’s very important so I want it done fast.
Cancer Research UK: How would you envision beta-blockers being used in the clinic?
Des Powe: Beta-blockers could be used as an ‘adjuvant’ therapy, meaning that they would support current treatments. You could potentially give beta-blockers to patients as soon as they are diagnosed and this might give protection against them developing secondary tumours.
Cancer Research UK: Beta-blockers are already in use so could they potentially reach patients faster than a completely new drug?
Des Powe: Yes. That should have a significant impact on the time spent in clinical trials.
Cancer Research UK: Is there any way of distinguishing patients that would respond to treatment with beta-blockers from patients who wouldn’t?
Des Powe: I would say that some of the most successful treatments for breast cancer are those that target specific molecules. The classic examples are Herceptin, which is targeted against HER2, and tamoxifen, which targets the oestrogen receptor.
So the patients whose tumours produce these receptors are, in theory, good candidates for receiving the targeted treatment and you’ve got a good reason to suspect that those patients will benefit from it. Beta-blockers neutralise adrenergic receptors, so you could identify the patients most likely to respond to them by testing whether their tumours produce these receptors.
Earlier this year, I found that tumours from around about 60 per cent of breast cancer patients produce one type of adrenergic receptor – the β2-adrenergic receptor. So theoretically, about 60 per cent of breast cancer patients could benefit from treatment with beta-blockers.
Cancer Research UK: You’re focussing on breast cancer in this study but could beta-blockers be used to treat other types of cancer?
Des Powe: Yes. Laboratory studies have shown that prostate, bowel and some types of lung cancer cells over-produce adrenergic receptors. This would suggest that these cancer types might respond to beta-blockers. But this will need to be confirmed.
Cancer Research UK: And finally, what inspires you most about your job?
Des Powe: I’ve always been interested in science and research is so challenging and exciting. I’ve always wanted to make an impact in fighting diseases – so it’s a reward coming into work!
Interview conducted by Safia Danovi, August 2011
Dr Des Powe October 10, 2011
Thank you for your comment and for sharing your own experiences with others. I appreciate that it must be an extremely difficult time for you and others in a similar position.
As frustrating as it sometimes is, good medical science has to follow highly disciplined and rigorous routes to safegaurd against possible harm and misleading claims. It is reassuring that the evidence supporting the use of beta-blockers in protecting against disease progression in certain types of cancer (breast and malignant melanoma) is accumulating. But, we need the results from larger and more powerful carefully controlled studies to validate these early findings. This way, we can channel our efforts into designing the most appropriate clinical trials that will produce the most meaningful and unambiguous outcome.
There are still questions to be addressed concerning the specificity of certain types of beta-blocker: it is probable that some patients will be better suited to these drugs, leading to targeted therapy. Research into this is on-going.
Coco October 1, 2011
Dear Dr Powe, I was diagnosed with strongly HER positive BC 16 months ago. I had been on anti hypertensives for 15 years but unfortunately NOT beta blockers containing propronol, the type the studies found to be most effective in reducing recurrences. I was on Atacand Plus an ace inhibitor which was one of the ones unfortunately associated with increased recurrence. It took me a few months to marshall the research papers and my arguments, see my GP and basically present my case for moving me from Atacand Plus to Noten. I was aware the studies were retrospective but I thought what the heck, I would be my own prospective study! I as already on anti hypertensives so taking one versus the other was not a big deal one way or the other and there were reasons for giving it a go – specifically your and others findings about BC recurrence being reduced by a statistically significant percentage. My suggestion is if you want a mid point prospective study that can get through the ethics and other approvals fast, then how about targetting women with BC who are already diagnosed with high blood pressure and taking non-propranol meds and get them to do what I have done – change over to propronol based anti hypertensive? This has the potential to move the issue along faster than waiting for human trial approval to give propronol based meds to women with BC who do not have high blood pressure. The stats are so amazing that I think this changeover is worth a try. Indeed many of us are already being our own guinea pigs based on your and others earlier research, without being involved in a formal trial. Internationally there may be enough of us already doing this for you to gather some useful data. Posts on the major international breast cancer websites asking for those of us already doing this to establish contact would be an effective way of reaching out and getting us on board.