An Anti-Cancer Polypill

The big health news story of the day is on the report that adoption of the 'polypill' - the proposed pill that combines a statin with three common blood pressure drugs. According to the authors of the study, rolling this polypill out to all over 50s will save tens of thousands of lives (I've seen different numbers in different reports, but they all agree it's a significant fugure). The rationale of the pill is that by taking these relatively cheap and non-toxic drugs lives will be saved by reducing the number of heart attacks and strokes. However, the effect should, in theory, extend to lives saved by preventing cancer. There's pre-clinical evidence that at least two of the drugs - simvastatin and losartan - have cancer prevention properties.

The idea of a polypill is one that I'll be exploring later in the year when it comes to cancer, and specifically for Li Fraumeni Syndrome and other hereditary cancer syndromes. An anti-cancer polypill would take simvastatin and losartan - one half of the current polypill - and add two additional drugs - aspirin and metformin. I believe that such an anti-cancer polypill has huge potential, both for the over 50s and also for people at high risk of cancer, including those who've been treated for the disease and are in remission.

As I said, this is an area that I'll be exploring in more detail in the future, so watch this space...

Dr Helen Hanson

Congratulations to Dr Helen Hanson, who is acting as the medical advisor to the George Pantziarka TP53 Trust. She has been appointed to a post of Consultant at the Royal Marsden Hospital, in London. One of Dr Hanson's plans is to start a specialist TP53 clinic at the hospital. This is a development we'll be following closely, and we'll report back as things develop in the future.

Biomarkers for Osteosarcoma Response to Chemo

Clinical advances in the treatment of osteosarcoma are rare, and as I have highlighted in the past (here, for example), there are no signs of improvements in outcomes in recent years. The standard treatment for osteosarcoma is neo-adjuvant chemotherapy (using multiple chemo drugs) to shrink the tumours and then surgery to remove them. One of the things that we do know about osteosarcoma is that good response to chemotherapy (defined as greater than 90% tumour cell death), is associated improved chances overall survival. In other words the more the tumour is killed by the chemo the more chance there is that the surgery removes it all and that there is a lower risk that it will have metastasised. However, assessing the rate of tumour kill is hard to do - at the moment you actually need to remove a sample of the tumour to analyse it. Unlike some other forms of cancer, there are no generally recognised bio-markers that you can use as a way of assessing the success rate during the chemotherapy treatment protocol. Nor is there any way of establishing which patients will respond well to chemotherapy and those that won't.

A just published study has looked at the relationship between the expression of the p16 gene in osteosarcoma and response to chemotherapy. The results were clear - loss of p16 expression in tumours is strongly correlated with a worse response to chemotherapy. This backs up previous work which looked at the relationship between p16 and survival in osteosarcoma. This new study now provides the link to explain this relationship. Lower p16 expression causes less sensitivity to chemotherapy, leading to less tumour cell necrosis and ultimately leading to worse outcomes.

This means that p16 expression can be checked at initial diagnosis and treatment options adjusted accordingly. For patients with high levels of p16 expression then the standard treatments will have more chance of success. For those with little or no p16 expression, other options will need to be considered.

Details of this new study are here: http://www.ncbi.nlm.nih.gov/pubmed/22578565

TP53 Trust - Update

This is just a small update to let people know about progress on setting up the George Pantziarka TP53 Trust. On the administrative side of things we are now set up with a bank account, have appointed the Trustees and are now in the process of registering with HMRC and the Charities Commission. Registering the HMRC (the inland revenue in other words), would mean that we would be able to claim Gift Aid on donations, which we can't do at the moment. Beyond that we want to register with the Charities Commission to get a charity number and formal recognition that we exist as a charity. The paperwork for all these is huge but unavoidable.

Aside from that we are continuing to make contact with more and more families. The stories are heart-breaking, but they underline why we need to create the Trust and the long way we have to go to provide support for people facing the most horrendous circumstances. The web site and forum get lots of visitors, but few seem to sign up and take part in discussions. This is something that will change with time, we hope, as the number of members increases we'll reach the critical mass required to turn the forum into a more viable proposition. In the meantime please drop by and say hello if you haven't already.

Aspirin and TP53 - Letter in British Medical Journal

There's been a flurry of papers recently on the effects of aspirin in cancer prevention. Some people have raised the possibility of prescribing aspirin to the general population, or at least everybody over a certain age. However, while the argument will go on for a while, there's some parts of the population in urgent need of cancer prevention strategies. In particular, people with a defective TP53 gene or Li Fraumeni Syndrome are at incredibly high risk of developing the disease and yet no research is being carried out on active measures to stop the disease occurring.

Aspirin might or might not make a massive difference, but even if it only makes a small difference that's still positive. What we need is the research to start now. And this is the point I make in a letter published today in the British Medical Journal. The letter can be accessed online here: http://www.bmj.com/content/344/bmj.e2480/rr/586138

This is an idea that needs to be pushed actively, and I hope to follow up with a more formal paper or article. The more we can do to kick start the research the better.

The Wrong Models of Cancer - Part 2

In the first part of this article I discussed one aspect of how researchers have modelled cancer in the test tube and how this has been a factor in the slow progress in 'the war on cancer'. To recap quickly, by ignoring the evolutionary processes taking place in cancer cell lines, in petri dishes and in implanted tumours, researchers are often surprised that what works in a lab doesn’t translate to the clinic. They’ve been targeting a different type of cancer cell to the ones that affect people. A tumour is more than a blob of a single type of deranged cell. It’s an entire eco-system of  'cancer' cells, the surrounding tissue (the stroma), disordered blood vessels, immune cells and so on.

But this is not the only type of wrong model. There is another that has had equally disastrous results – and it begins with the very phrase 'the war on cancer'. This metaphor of cancer as a war reflects the belief that the only way to deal with cancer is to eradicate it completely. Cancer cells have to be destroyed once and for all, and therefore the most radical and demanding treatments are used. Our current range of cancer treatments are some of the most demanding and dangerous in medical practice. Radical surgery, toxic chemotherapy, burning with radiation… These treatments are barbaric but it’s the best we have so long as the intention is to go in and kill every single cancer cell that exists.

BBC Catches Up With Anticancer.org.uk

I know that's a bit of a cheeky title, but I do feel the need to point out that today's story on the BBC website: 

Curry's ability to fight cancer put to the test

is about the curcumin and chemotherapy trial that I wrote about here on the 19th December 2011:

http://www.anticancer.org.uk/2011/12/curcumin-trial-in-uk.html

In any case, it's a story worth keeping an eye. Of the many naturally derived substances that show anti-cancer ability, curcumin is one of the most promising, but also one of the most problematic. As a single agent it clearly doesn't have a strong enough anti-cancer action, even at high doses, so combining with other agents, like standard chemotherapy drugs, is a good strategy.

Ultimately though, I strongly suspect that it will be engineered molecules that are derived from curcumin that will make it into the clinic first. There are already different curcumin analogs showing promise in animal models - though none have made it to patient trials so far.