LFS - Primed for cancer - Interview

The excellent Living LFS blog has a new piece which covers my latest  paper on Li Fraumeni Syndrome...

http://livinglfs.blogspot.co.uk/2015/05/primed-for-cancer-with-pan-pantziarka.html

This explains the core details of the paper in very non-technical language and explains what it may mean in practice. So, if the technical nature of the original paper gets in the way, then this is certainly a good alternative.

Press release - Primed for cancer?

Li Fraumeni Syndrome (LFS), a rare genetic condition that predisposes sufferers to cancer development, is associated with mutations in the TP53 tumour suppressor gene. Although rare, LFS sufferers have a highly elevated risk of developing one or more cancers, with some estimates putting the life-time risk at 70% for males and 100% for females. However, new research published today in leading online oncology journal ecancermedicalscience, suggests that cancer development may be due to more than a mutated tumour suppressor function.

In a new paper by Pan Pantziarka PhD, a scientist working for the Anticancer Fund and co-ordinator of the Repurposing Drugs in Oncology(ReDO) project, it is suggested that there are other important functions of the TP53 gene that contribute to this elevated cancer risk. 'Our knowledge of the multi-faceted functions of TP53 has grown enormously in the last few years,' Pantziarka says, 'yet much of this new information has yet to be integrated into our understanding of the disease process in people with LFS'.

Sue Armstrong, author of 'p53: The Gene that Cracked the Cancer Code', points out that: 'TP53 is the most commonly mutated gene in human cancer. Indeed it’s probably fair to say that if this key tumour suppressor is functioning properly, it’s almost impossible for cancer to develop. It follows that to be born with mutant - and therefore malfunctioning - TP53 in every cell in the body is to be extremely vulnerable to cancer. This is the tragic fate of people with Li Fraumeni Syndrome, for whom conventional therapies rarely offer more than temporary respite. So, new ways of looking at, and treating, cancer are sorely needed.'

Known as the 'guardian of the genome', the p53 protein is at the heart of an array of signalling networks involved in responding to DNA damage, metabolic stress, immunity, senescence and ageing. In people with normal p53 function, the kinds of damage that cause cells to become cancerous trigger a damage response that normally leads to the cell self-destructing before it can proliferate, a process called apoptosis. But in people born with a mutated TP53 gene this process does not take place. However, there is more to cancer than delinquent cells, increasingly we understand that cancer also involves a supporting micro-environment to provide a blood supply, nutrients, protection from an immune response and so on. These factors may also involve p53, and Pantziarka's hypothesis suggests that people with LFS are born 'primed for cancer' because many of these cancer-support systems are already in place thanks to the mutation.

Pantziarka has first-hand knowledge of this disease process himself, having lost his first wife and his teenage son, George, to cancers due to LFS. George, for example, developed his first cancer at the age of two and subsequently developed two further primary cancers before succumbing to metastatic sarcoma in 2011. The story is told in a recent book, 'For The Love of George' by Irene Kappes, available from Amazon and other booksellers. The family have also established the George Pantziarka TP53 Trust (www.tp53.org.uk) to provide support for other families and to promote research into the condition.

This new hypothesis does more than provide a more nuanced view of cancer development in people with LFS, it also suggests that many of these additional factors may be amenable to drug treatment. 'By expanding our view of carcinogenesis in LFS we may also be broadening the range of interventions available to us to change things. The key thing,' Pantziarka underlines, 'is to start looking at active measures we can take to reduce this risk. Drugs such as metformin may hold the promise of reducing that life-time risk by some significant margin.'

In perhaps the most radical section of the paper, it is suggested that some other cancer predisposition syndromes, caused by mutations in other genes, may share some of the same features of LFS despite the different genetic drivers. If this is the case, as the paper suggests, then perhaps some of the active measures which warrant investigation in LFS may also apply to a range of different genetic cancer predisposition syndromes. In such a case the prospect of a clinical trial that targets multiple high-risk patient populations is an alluring prospect. 'With limited population sizes it is difficult to design cancer-prevention trials because the sample sizes are too low,' Pantziarka explains, 'but if my theory is correct then we can pool different populations into the same trial and look for reduced cancer incidence across the board.'

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Links/Contacts:
The George Pantziarka TP53 Trust – www.tp53.org.uk
Original paper (publication date 21/05/15): ‘Primed for cancer: Li Fraumeni Syndrome and the pre-cancerous niche’ -http://ecancer.org/journal/9/541-primed-for-cancer-li-fraumeni-syndrome-and-the-pre-cancerous-niche.php

Book Review - p53 : The Gene That Cracked The Cancer Code

Keywords: Cancer, p53, Li Fraumeni Syndrome Title: p53 : The Gene That Cracked The Cancer Code Author: Sue Armstrong Publisher: Bloomsbury Sigma ISBN: 978-1472910516

Buy US Buy UK

If any single gene deserves a biography, it’s TP53 (more commonly known as p53). This is the gene, memorably christened the ‘guardian of the genome’ by David Lane, one of its co-discoverers, which is the tumour suppressor that is most commonly lost or mutated in cancer. It’s also the gene most commonly mutated in the rare and deadly cancer predisposition condition called Li Fraumeni Syndrome. Science writer Sue Armstrong has crafted that biography, delivering a book that is engaging, interesting and has a real page-turning quality that you might not expect for a book on the workings of a single gene.

Adopting a largely historical narrative, the book explores the evolution of our understanding of cancer via our expanding knowledge of p53. Early on, before the structure of DNA was unravelled, scientists explored the viral transmission of cancer in animal models – sarcoma viruses could reliably infect animals with tumours. If it worked for animals, they reasoned, why not for people? How did the virus create tumours? Investigations showed that these viruses triggered changes in cells that eventually developed into cancers. Individual genes and pathways were discovered that were termed oncogenes – these were the culprits that caused cancer.

But of course most cancers that develop in people are not virally transmitted, but as technology and scientific tools expanded the theories developed and changed. Our understanding of DNA spawned a revolution in our thinking, including our thinking about cancer and the role of genetic change. When it was first discovered – independently by multiple groups – p53 was assumed to be just another oncogene, a driver of cancer development.

For The Love of George - Book

The starting point for this blog was a conversation with my son, George, in the middle of his battle with osteosarcoma. I’d had been immersed in reading about treatments, supplements, theories and he thought that it would be good to share that knowledge with other people. We talked about it for a while and he came up with some ideas for a logo, we talked about the domain name and so on. It was typical George, thinking about the future, coming up with plans and schemes. The other web site he was really keen on starting was eat positive, that was one he was really keen on and I’m glad that I’ve managed to kick that off in a very low key sort of way too. Unfortunately not every story has a happy ending, and George did not live to see either of these sites become real. And of course after his death we created the George Pantziarka TP53 Trust to support other individuals and families afflicted with Li Fraumeni Syndrome in the same way that he was.

But for all this activity, I do sometimes worry that people will lose sight of who George was. He was a kid who suffered three different cancers, and who tried just about every treatment available before finally succumbing to the disease at the age of 17. It’s a painful story, but one that is common to families with LFS, or to families with a child with cancer. It’s a story that needs telling. And to that end my wife, Irene Kappes, has written a book called ‘For The Love of George’. I’ll be honest, it’s not an easy read. It doesn’t have a happy ending, though we all hope that what we are doing in his name can make something positive out of what he went through.

We worry that the book is harrowing and will scare some people, but then how can we make clear what families with LFS have to go through if we’re not honest? The only way is to show what George was like. To show what a fantastic kid he was, how we had good times even when the medical situation was grim, and to hope that there things in the book that people can learn from.

A portion of the proceeds from the book will go into the Trust.

The book is available on Kindle and as hard copy from Amazon.

In the UK: Kindle or Paperback

In the US: Kindle or Paperback

Li Fraumeni Syndrome and Cellular Metabolism

A while ago I wrote about the trial of the anti-diabetic drug metformin  in individuals with Li Fraumeni Syndrome (LFS) and the importance of starting to look beyond the idea that LFS is just about a defects in the self-destruct mechanism of damaged cells. Another clinical trial in LFS, also at the National Institutes of Health in the United States, is also taking place and this one too is about looking at a different aspect of LFS. The ‘Role of p53 Gene in Metabolism Regulation in Patients With Li-Fraumeni Syndrome’ study (http://www.clinicaltrials.gov/ct2/show/NCT00406445) is looking specifically at whether a mutated TP53 gene causes metabolic changes in humans, as it does in mice and in test tube studies.

This is not just an academic question – ultimately we are looking to see whether there are factors that can change the cancer risk in individuals with LFS. This is the key idea in my own research on LFS, see for example the paper on ‘Li Fraumeni syndrome, cancer and senescence: a new hypothesis’.

Dr Paul Hwang, one of the investigators on this new trial kindly agreed to respond to a few questions on his work:

Pan: In your experiments you have found that mice with a mutated TP53 gene show different patterns of cellular metabolism compared to mice with non-mutated TP53. How would this difference manifest itself day to day? For example, would you expect to see different responses to exercise and diet?

PH: In a preliminary study of individuals carrying mutations in the TP53 gene (encoding p53 protein), we have observed evidence of increased muscle oxidative metabolism which is carried out by sub-cellular compartments of the cell called the mitochondria. In a mouse model of LFS, where genetic and environmental variables between individuals can be well controlled, we see a marked increase in aerobic exercise capacity which is also dependent on muscle mitochondria. Thus, in individuals with LFS this intrinsic characteristic could manifest itself as higher baseline endurance exercise capacity. Additionally, with exercise training, it could be possible to see a more robust improvement in fitness compared to individuals who do not carry the TP53 alteration. However, it should be noted that there are many different mutations of TP53 that can cause LFS, and it is not known whether our finding of increased oxidative metabolism is applicable to all individuals with LFS. With respect to diet, we have observed that some p53 mutations result in unresponsiveness to nutrient deprivation at the cellular level but how this affects the relationship between diet and cancer in people would only be speculative at this time.

Guest Post - Genetic Alliance UK: The My Condition, My DNA Project

 My Condition, My DNA

Would you be willing to take part in a research study to help us understand what patients affected by genetic conditions and their families think about the use of genomic sequencing in the NHS?

When the first person had their entire DNA sequenced as part of the Human Genome Project back in the 1990s, it took over 12 years. Today it is possible to have your entire genome sequenced in just a matter of weeks. A new technique has been developed which means it is faster and cheaper to do this, and as a result has the potential to dramatically change the way that conditions may be diagnosed and treated.

The aim of this research is to find out what patients and families think about genomic sequencing. This will involve exploring the ethical, societal and practical issues raised by the NHS using genomic sequencing to collect large amounts of an individual’s genetic information with the view to improving healthcare. As the ease of genomic sequencing and its potential uses becomes greater, people working in the NHS and other healthcare providers will be thinking about these issues and making decisions. By being a part of this research, you can help to bring the perspective of patients into the decision making process and form a key part of shaping how genomic sequencing could be used in UK healthcare to benefit patients.

What is the purpose of this project?

To help patients and their families understand what genomic sequencing is and how it might be used in a healthcare setting; and to understand from them their opinion of the ethical, societal and practical issues raised by using genomic sequencing in the NHS.

Who can take part?

If you or a member of you family has a diagnosed or suspected genetic condition we would like to hear from you. We are particularly interested in having families take part. This may include children under the age of 18, although an individual under 18 cannot take part without a parent or guardian.

LFS - Trial of Metformin

One of the implications of the 'two compartment' hypothesis of Li Fraumeni Syndrome (LFS) is that having a TP53 mutation is not necessarily a guaranteed route to cancer. The theory suggests that there's more to the syndrome than a damaged tumour suppressor gene, and that the 'host environment' is just as important. And what is the host environment in this context? It's the internal state of the body. The theory suggests that cancer risk is a function of damaged TP53 gene and certain conditions which are conducive to cancer. Change those conditions and you reduce the risk of cancer in LFS. In the paper where I introduced the hypothesis I suggested that one possible mechanism to make a positive change to reduce the risk of cancer in LFS is through the well-known anti-diabetes drug metformin. So, late last year the George Pantziarka TP53 Trust put in an application to run a cancer-prevention trial in LFS using metformin. Unfortunately we were unsuccessful in gaining funding for that trial, partly because a cancer prevention trial is actually a hard thing to accomplish, particularly in a rare condition like LFS.

However, a new trial is taking place in the United States looking at the short-term impact of metformin in people with Li Fraumeni Syndrome. The full details of the trial can be accessed here: http://www.clinicaltrials.gov/ct2/show/NCT01981525

The aim of the trial is to track what happens to a range of insulin-related blood markers in LFS patients over a 20 week period, with 14 of the 20 weeks on metformin and with biomarkers checked at regular intervals. The intent of the trial is initially to assess changes in these biomarkers and to assess whether daily metformin is tolerable or not. Now there's no reason to believe that daily metformin would not be tolerable, after all this is a drug that type II diabetes patients take for years on end, but when looking at a specific population of patients like this a trial has to be done. The more important thing is that the trial will be tracking these insulin related markers - specifically plasma insulin, IGF-1 and IGFBP3 - which are associated with increased cancer risk.

As important is the fact that this is that very rare thing, a trial in LFS, and the mechanics of making this happen are important. Being able to recruit and follow patients is a key factor in whether trials go ahead or not. We all need to make sure that this is a trial that is successful so that it can be used as a model for future trials.

So, if you're in the US and you have LFS, then please take a look to see if you are eligible. After all, we can never get to fully-fledged multi-year cancer prevention trials in hereditary cancer conditions like LFS if we can't even make small short-term trials work successfully.

Probiotics and Cancer Risk

The link between diet and cancer is complex enough for most people, but add in a genetic predisposition to cancer and the complexities go through the roof. While there are plenty of people out there with healthy diet plans and advice on what to eat to avoid cancer, when it comes to family histories full of cancer, doesn’t genetics trump diet? Is it really possible to reduce your cancer risk in spite of your family history? I am convinced that genes do not rule your destiny. Indeed one of the key things in my two compartment theory of Li Fraumeni Syndrome is that there are ways to massively reduce the risks of cancer even for people with mutated TP53 tumour suppressor genes. The same applies to women with BRCA1 or BRCA2 mutations – while there’s a definite elevated risk of cancer, it does not mean that there’s nothing that can be done to reduce the risks.

Which is why a recent paper published in the International Journal of Cancer makes for such interesting reading.  The title of the paper pretty much says it all:

Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice

Sadly this is not an open access paper that we can all read online. However, the authors of the paper had previously looked at the influence of probiotic bacteria on obesity, and that paper is accessible to all for those who are interested:

Microbial Reprogramming Inhibits Western Diet-Associated Obesity

In that work the authors fed mice a conventional ‘fast food’ diet and monitored the response – a set of obese mice. In contrast mice fed the ‘fast food’ diet but with added pro-biotic yoghurt avoided the onset of obesity, despite eating the same ‘fast food’ diet high in fat, sugar and low in vitamins and fibre. The addition of the yoghurt counteracted the pro-inflammatory effects of the poor diet.

In a detailed set of experiments the authors moved from looking at yoghurt to looking at the probiotic bacteria in the yoghurt, particularly a strain of bacteria called Lactobacillus reuteri. Mice fed the bacteria, in water and without the yoghurt, were still protected from the onset of obesity, and that the immune system was a key component of this positive effect.

In this latest paper the authors again use this beneficial probiotic but in this case they look at cancer development in mice. First they compared cancer development in mice fed the ‘fast food’ diet and those fed a more normal mouse diet. And, as you can probably guess, the ‘fast food’ diet was associated with both obesity and a higher incidence of breast cancer than the control diet. No surprise there. But the addition of probiotics to the diet reduced both cancer incidence and the size and growth rate of tumours that did develop. Now here’s where we get the surprise, because why should adding probiotic to the diet and helping the good bacteria in the gut, have an influence on breast cancer development?

The authors took this work a step further and then used mice with a genetic predisposition to breast cancer and fed one set the ‘good’ diet and the other set the ‘good’ diet with the probiotic. Now in these mice even the good diet led to cancer, though of course there was no obesity involved this time. However, and this is why this is such a great piece of news, the mice who also received the probiotic had lower cancer incidence, slower growing tumours and a longer survival time. In other words in spite of their genetic make-up there was a degree of protection from cancer just with the addition of a probiotic.

The papers go into much more detail on the mechanisms at work, principally to do with different classes of cells in the immune system, but that key result really stands out.

There are the usual caveats about extrapolating from mice to humans, but there is some evidence in people that yoghurt consumption can have a protective effect, both in obesity, metabolic syndrome and cancer. The next step is to take this work to another level and to start thinking about clinical trials. There are lots of ways we can test this out. For example, how about a trial in women with high risk of breast cancer recurrence? Or a trial in women with a genetic predisposition to cancer? And what about some work to see whether this protective effect can apply to other cancer types?

And, of course, there is nothing to stop people adding live pro-biotic yoghurt to their diets, or even taking pro-biotic tablets or drinks if they don’t like yoghurt.

The Promise Of SIGNIFY

One of the good things about writing on cancer is that you get to meet or make contact with people from all walks of life, of all ages and from all over the world. Really, when it comes to cancer, all human life is here (which sounds weird, I know). I wanted to start 2014 with a story of a recent contact via the George Pantziarka TP53 Trust because it’s so positive.

I first wrote about the SIGNIFY trial back in August 2012 (http://www.anticancer.org.uk/2012/08/signify-new-uk-lfs-study.html). This is a trial of a new screening protocol for people with Li Fraumeni Syndrome. Instead of waiting and watching for cancer, the idea is that people are proactively screened using whole-body MRI hoping to catch malignancies before they develop. Recruitment started in early 2013 (http://www.anticancer.org.uk/2013/02/lfs-signify-trial-looking-for-volunteers.html). And just before the New Year I was contacted by a young woman called Lara, who was participating in the trial. Her case epitomises the promise of SIGNIFY.

Lara attended her MRI screening at the Royal Marsden Hospital and was then asked to return for a rescan of the liver and kidneys. She assumed that this was nothing out of the ordinary – she was suffering from no symptoms and felt fine. Instead the scans discovered two primary tumours – one on the liver and another on a kidney. Without the routine scans of SIGNIFY these two tumours might not have been picked up until it was too late to do anything about them. As it is she faces surgery at a time when resection is still possible and is still the best treatment.

As Lara herself has told me:

If I hadn't got tested right when I did I think my story would be a very different one. A year earlier and they may not have been picked up at all, a year later it might have been too late. 

We can but hope that in time the SIGNIFY trial will lead to permanent changes in cancer surveillance for people with LFS. We can hope that it will pick up disease before it becomes life threatening. We can hope that it will save lives. It’s too late for George and Kane and other young LFS sufferers who were diagnosed too late, but we can hope that their stories are not repeated in another generation of young people.

In the meantime I wish Lara, and the rest of the people on the George Pantziarka TP53 Trust forum, the very best for 2014.

Li Fraumeni Syndrome - A New Hypothesis

In the last year or so I have been working on developing some new ideas on cancer development in Li Fraumeni Syndrome. The results so far are a paper in a peer-reviewed oncology journal (Cancer Cell International), and a follow up article (aimed at clinicians rather than researchers) in Oncology News. Both of these are open access publications:

My paper is available here: http://www.cancerci.com/content/13/1/35

And the less technical version is here:: http://www.oncologynews.biz/pdf/20%20ONJA13/88_JA13_Li%20Fraumeni%20Syndrome.pdf

But this isn't the end of the story - I am continuing to develop these ideas and follow up on the clinical implications.

George - Second Anniversary

One of the many doctors who treated George described him as a miracle child. And it was true. He had survived a rhabdomyosarcoma diagnosed at two and which was aggressively treated for about a year, followed by a few months in remission. When the disease recurred it was treated hard again but the last scan showed there was still evidence of disease. With no options left on the table we were sent home to prepare for the worst. George was just four years old. We refused to accept the news, and he was just a kid who wanted to play. And play he did, for the next eleven years. He really was a miracle child. But when he was fifteen he was diagnosed first with a basal cell carcinoma and then, a little later, with osteosarcoma. For us the miracle ended two years ago, when the osteosarcoma finally defeated our wonderful, lovely child, after the hard years of battle.

On this second anniversary it’s time to take stock of where we are with the Trust formed in his name. One of the things we wanted to focus when we started was on encouraging more research in Li Fraumeni Syndrome. We never imagined that we would be responsible for some of that research, but that is precisely what has happened. Over the last year I have developed a new theory about cancer initiation in LFS, one that is subtly different from the mainstream view. The first test of a new theory is to see if it can stand the peer review process and be published in a reputable peer-reviewed scientific journal. I am happy to report that the paper ‘Li Fraumeni Syndrome, cancer and senescence: a new hypothesis’ has been published in the journal ‘Cancer Cell International’. There will be more to say in the coming weeks and months about this paper, but for now it’s available for download at the journal’s website.

Ablation of bone tumours

For patients with advanced cancer bone tumours, (whether from primary bone cancers like osteosarcoma or metastases from other types of cancer, such as breast or prostate), can be a cause of persistent and hard to treat pain. A standard treatment in many such situations is radiotherapy, which can have unpleasant side-effects, and, in the case of Li Fraumeni Syndrome patients, might also have long-term implications regarding further cancers. Additionally, treating cancer pain with opiate-based pain-killers, such as morphine, can also be problematic given the evidence that opioids can cause further cancer progression (though this can be reversed with the use of naltrexone).

In which case there’s some encouraging news being reported at the 29th Annual Meeting of the American Academy of Pain Medicine. A group of French clinicians have reported on treating patients with tumour pain, including bone tumours, with micro-wave ablation (MWA).

One of the doctors, Adrian Kastler of the Centre Hospitalier Universitaire, in Besançon, France, is reported as saying:

"This technique may be applied to any patient suffering from bone tumour pain, mainly in patients suffering from bone metastases, refractory to conventional therapies. The main advantage of ablation techniques is the fast pain relief obtained - immediately after the procedure - as opposed to delayed pain relief obtained with radiation therapy… Our research showed that the use of MWA in bone and soft-tissue tumours is feasible and effective concerning pain palliation. However, MWA needs to be studied in order to apply the same procedure in a curative intention." 

The last point is certainly one that needs urgent attention. Bone tumours are notoriously hard to treat, so any new treatment that shows signs of being effective needs to be researched as a matter of priority. And, given that primary bone cancers are often unresponsive to chemotherapy, any physical treatments that can be used alongside surgery are urgently needed.

LFS SIGNIFY Trial Looking for Volunteers

This just in from the people running the SIGNIFY trial for Li Fraumeni Syndrome:

We are conducting a small scale pilot study to investigate the use of whole body magnetic resonance imaging (MRI) in families with Li Fraumeni Syndrome.

We would like to enrol individuals in the trial who are between 18 and 60 years old and are known to have a genetic mutation (alteration) in the P53 gene as well as unrelated people who do not carry the gene mutation whose scan results can be used as controls.

All study participants will undergo a whole body MRI scan at the Royal Marsden Hospital, Sutton, Surrey.

If you are interested please contact SIGNIFY study coordinator Dr Emma Killick or another member of the SIGNIFY team at the Institute of Cancer Research on 0208 661 3375.

Irreversible Electroporation

The three main arms of cancer treatments remain surgery, chemotherapy and radiotherapy - these still form the core treatments for most cancers. Arguably the set of treatments called ablative therapies should be added to that list. These include photodynamic therapy, cryoablation, and radio-frequency or microwave ablation. While these treatments work in different ways, they have some common features, they all:

• physically attack tumours (with heat, cold, laser light etc.)
• can be re-applied (i.e. resistance to treatments doesn't set in)
• side-effects are local and easily controlled
• are little used compared to surgery, chemo and radiotherapy

The last point is an important one, as these treatments have excellent safety profiles and can be targeted to achieve good rates of local control of tumours. The downside is that these treatments have to be applied to individual tumours rather than being able to systemically control widely spread disease. However, when used with other treatments these ablative treatments can make a huge difference to outcomes. As a bonus, for those with mutated tumour suppressor genes like TP53 (i.e. patients with Li Fraumeni Syndrome), there are no unwanted long term risks of other cancers due to DNA damage in surrounding tissues.

SIGNIFY - New UK LFS Study

I am happy to be in a position to confirm that a new UK study will look at active surveillance for Li Fraumeni Syndrome patients. The SIGNIFY study, which is now at the final stage of approval, is being run by the Institute of Cancer Research and will initially be available at two centres, Manchester and the Royal Marsden. The protocol will look at the effectiveness of annual whole body and brain MRI scans in confirmed LFS patients. A secondary part of the study will look at the psychological impact of screening.

Recruitment to this new study hasn't started yet, and there is a possibility that it may change slightly before it gets complete approval. As soon as the trial is confirmed and we have some more concrete information details will be posted here. The people running the study are in touch with the George Pantziarka TP53 Trust and will keep us informed.

Aside from anything else, this is a good example of how the forum on the Trust's web site is turning into a valuable tool. The first mention of the proposed trial surfaced there last week, and now we have official confirmation. Thanks to all those who first raised the alert.

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.

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.

Introduction to LFS - Leaflet

One of the things that sufferers of Li Fraumeni Syndrome have to deal with is the complete lack of knowledge of the condition amongst most people. This is especially irritating when it includes doctors, nurses, health visitors and so on, as well as teachers, health visitors and so on. It takes time and energy to keep having to explain what TP53 is and how it can cause LFS and so on. As one way of short cutting all of this the George Pantziarka TP53 Trust has just published an introductory leaflet that can be downloaded, printed off and passed around to those people who want to know more or who need to understand what it means for sufferers.

The PDF can be downloaded directly from the site here: http://www.tp53.co.uk/index.php/lfs-leaflet