Friday 7 December 2012

Online Petition in Support of Henry Mannings

Everybody following the story of Henry Mannings, is urged to sign the online petition in his support:

Tuesday 4 December 2012

A Medical Outrage

Imagine that you are suffering from a rare and aggressive form of cancer, and after the failure of all your treatments you find yourself days away from death. Unwilling to just give up and die you seek out a different treatment and, miraculously, things stop getting worse and start to turn around. This isn't a miracle cure - the cancer is still there - but you start to gain strength, you become more mobile, you have stepped away from the brink. Now imagine that if the only doctor who could prescribe this treatment was suddenly stopped from giving it to you. Your life line has just been snatched away.

That's a pretty horrible picture I've just painted, but this is exactly the position that Gary Bowden, suffering from a rare bone cancer called chondrosarcoma, finds himself in. The treatment that has pulled him off the Liverpool Care Pathway is Coley's Toxins, prescribed by Dr Henry Mannings at Star Throwers in Wymondham, Norfolk. Dr Mannings is the only person in the UK licensed by the MHRA to give Coley's to his patients. Yet because of a completely unrelated complaint Dr Mannings has been banned by the GMC from prescribing drugs at Star Throwers. Effectively this is the end of treatment for Gary Bowden and the other patients receiving Coley's.

The whole thing stinks. It's an outrage that patients with no other treatment options are being denied a treatment that is working for them. Not one patient has ever complained about Dr Mannings and his treatments - not one.

I am proud to be a trustee at Star Throwers, and I've seen the statement that Gary Bowden wrote to the GMC prior to the hearing against Dr Mannings. It's a catlogue of misdiagnoses, poor treatments and worsening disease. The failure to diagnose his disease for two years doesn't have any spin-offs, but Henry Mannings prescribing at Star Throwers does. It's an outrage.

You can read more about Gary Bowden here:

Wednesday 28 November 2012

Dr Henry Mannings and the GMC

There have been a number of reports in the press and on TV about Dr Henry Mannings and Star Throwers. I have written about Dr Mannings and his use of Coley's Toxins before. In my opinion he is above reproach and the case against him without foundation. The following is a statement that has been issued by Star Throwers, the cancer charity that Dr Mannings founded, and where I am glad to serve as a trustee.
Star Throwers would like to make it fully clear from the outset that we understand the purpose of the GMC Interim Orders Panel is to ensure patient safety, which we are in full agreement with.

Dr Mannings attended a GMC Interim Orders Panel hearing on Tue 27th November 2012, after which the GMC have concluded that there are no grounds for suspension. They have, however, decided to restrict Dr Mannings' prescribing of medication to within NHS premises only.

Star Throwers charity will remain open as usual, with Dr Mannings continuing to offer advice and support to cancer patients and their families.

The restriction is based on the allegations of one oncology consultant at one hospital, and is despite the fact that the two patients mentioned in the allegations had significantly benefitted from the therapy they had received from Dr Mannings. At no time have there been complaints from any of Dr Mannings’ patients or their families.

The loss of prescribing ability at Star Throwers is a loss to many of the patients who have been given up on by their own oncologist.

It is important to note that the IOP's decision is based "on the interest of patient safety" and has no bearing regarding any findings of fact or the veracity of the allegations.

Although we are not allowed to discuss the details of the Interim Orders Panel's decision report, we find the decision made by the panel difficult to understand considering the overwhelming evidence produced in favour of Dr Mannings, particularly by experienced senior oncologists, a professor of oncology, nurses and pharmacists.

We hope that there will be a full public GMC hearing, whose purpose is to decide the veracity of the allegations, within the next 18 months so that the true facts of this case will become evident.

Dr Mannings would like to express how touched he is by the hundreds of letters written and phone calls in support of Dr Mannings and all the staff at Star Throwers.

Monday 26 November 2012

In the PINC - stopping the reverse Warburg Effect

There was an interesting report recently on some work in the US looking at the use of a common anti-malarial drug and breast cancer. The drug in question is chloroquine, which is both cheap and widely used throughout the world. Aside from its action against the parasite that causes malaria, the drug is also known as an inhibitor of autophagy, which is a cellular state in which the cell digests parts of itself, normally as a survival mechanism in the face of lack of nutrients or damage to cell components. 

The study in question is called the PINC trial (Preventing Invasive Neoplasia with Chloroquine), which is specifically looking at women with ductal carcinoma in situ (DCIS), which is a pre-cancerous condition that is often picked up through breast screening. DCIS has the potential to progress to fully blown breast cancer. Part of the problem of the over-diagnosis of cancer associated with breast screening is that currently there is no way to be sure which DCIS lumps are going to become life-threatening cancer and which will remain harmless. The PINC trial is about treating women with DCIS who are waiting for surgery with chloroquine for four weeks and then to assess the effect this has on the DCIS lump. More details on the trial are available here:

While the trial has yet to report it’s findings, the initial signs are looking positive. If chloroquine can stop DCIS lesions from developing into invasive cancers that would be a major step forward for women. Stopping cancer before it develops is a much better strategy than simply turning every woman with a DCIS lesion into a cancer patient because you don’t know how the lesion is going to develop.

Tuesday 20 November 2012

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.

Friday 19 October 2012

Mebendazole - Tumours and Tapeworms

There’s a big push by some in the cancer research community to look at old drugs to see if they’ve got some anti-cancer activities. It makes a huge amount of sense to do this as it short circuits all of the phase I trials to test a drug’s toxicity, often these drugs are cheap generics and there’s many years of data on pharmacokinetics and side effects and so on. It means that in a best case scenario you can cut out years of preliminary work. Some of the drugs, like the anti-diabetic drug Metformin or plain old Aspirin also have evidence of anti-cancer effects in the population rather than just from test-tube experiments or computer simulations. And the good news is that the list of such drugs is growing longer by the day, and the evidence continues to mount up that some of the best candidates will enter use soon either as support to existing treatments or, in some cases, as part of new protocols to prevent recurrence of disease after treatment.

One of the more surprising drugs in Mebendazole, an old drug that has been around for a long time as a treatment for parasites like tape-worms. Mebendazole, which is available over the counter in any case, has got a surprising amount of evidence in its favour as an anti-tumour drug. This evidence comes from modelling the molecular profile of the drug to see how it fits with particular cancer pathways, from experiments in test tubes and in animal testing using human tumours. As pre-clinical evidence goes, that’s pretty much the works.

Thursday 13 September 2012

Fund-raising In George's Memory

Once your child is diagnosed with cancer your world changes forever. Aside from the immediate shock, you find yourself and your child immersed in a nightmarish environment of hospitals, treatments, stress and worry. Even the nature of time changes once you enter into treatment - days blur into each other in hospital, respites at home seem to fly by, and there's the endless waiting - for appointments, for drugs, for scans and for results (which is the worst of the waiting). After a while you learn to navigate through the ins and outs of the medical system, working out what you can and can't do, what services exist and where you can find them and so on.

Like a lot of families in that situation we found that there was one organisation that helped us found our way and that was the children's cancer charity CLIC Sargent. The help they offered was purely practical - finding out what we could do about schooling will George was having chemo, helping to sort out the endless paperwork that comes with the territory (and believe me, some of the forms we had to deal with would have been horrendous at the best of times, let alone when dealing with cancer), offering a shoulder to cry or helping us find the best person to deal with specific questions.

Maureen and the rest of the CLIC Sargent team at the Royal Marsden is Sutton were just fantastic. So when asked to nominate a charity for some fund-raising in George's name they were the first name to come to mind. If we had been further along in organising the George Pantziarka TP53 Trust the fund-raising by my colleagues at work would have been for that. But given where we are, there's no doubt that CLIC Sargent deserve your support.

So, please take a look at the ISG Clarendon Relay Marathon Team Challenge here: and help raise some funds for a very worthy cause.

Wednesday 12 September 2012

Chemo, Radiotherapy and Fasting

A while back I wrote about some work by Valter Longo and his colleagues looking at the effects of short-term fasting on cancer progression (here: They showed that short term fasting can slow tumour progression in a range of different cancer types and can sensitise tumours to standard chemotherapy drugs. While this work was performed in mice, it was solid research that is already being followed up in a number of clinical trials.

In the latest update to their work, Dr Longo and his team report that short term fasting also helps to sensitise cells to radiotherapy. This time the work looked at gliomas - aggressive brain cancers - again in mice. This time they looked at how the standard treatments for gliomas, including glioblastoma multiforme, were improved by the adoption of short term fasting. Both chemotherapy (Temozolomide) and radiotherapy had improved responses in those mice subject to complete withdrawal of food for short periods (48 hours) compared to control groups.

These results are in mice, but again there is no reason why they should not apply to people. Though whether there is the same degree of response is an open question which can only be answered through clinical trials.

For the moment this is yet another small step forward and confirms once again that cancer is more than a disease of delinquent cells, and that disordered metabolism is a key feature with clinical significance.

For those wanting the full details of this new research, it has been published in the open access journal PLOS One:

The final word has to be this. If you're a cancer patient and want to try this out for yourself, make sure you talk to your oncology team to ensure you get the support you need.

Tuesday 28 August 2012


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.

Thursday 16 August 2012

Peripheral Neuropathy and Chemotherapy

Side effects from chemotherapy can often be worse than the symptoms of cancer itself - as many patients know, and as we know from our experiences with our son George. For taxane-based chemotherapy, such as Taxol, Paclitaxel and Docetaxel (which is one of the drugs that George had), one of the worst side effects is called peripheral neuropathy. This involves nerve damage, particularly in the hands and feet. It usually manifests as tingling, numbness, burning or pain, but can also involve blood pressure changes, balance problems, constipation and a range of other problems.

It can be severe, and in our case it got so bad that George ended up having to come off treatment, with disastrous results in the end. Again, this is common, and so-called 'dose limiting toxicities' mean the treatments are scaled back or stopped, even when they are showing some signs of effectiveness. Obviously, finding good ways to stop the side-effects means that patients can continue with treatments, and also their quality of life doesn't descend into misery.

Which makes the results of a recent clinical trial worth noting. This was a randomised placebo-controlled trial - which means some patients got the treatment and some got a dummy pill and then the two groups of patients were compared to see what difference the treatment made. The trial was specifically looking at peripheral neuropathy in cancer patients being treated with Paclitaxel. And the treatment being tested? Omega-3 fish oil capsules three times a day. Yep, good old fashioned fish oils rather than some fancy new drug.

The results? 70% of the fish oil patients didn't get peripheral neuropathy, will in the control group it was only 40% that didn't. Not only that, there was a clear tendency for the symptoms to be less severe in the fish oil group for those patients who did suffer some symptoms.

Given all of the other positive benefits of fish oils, this is certainly a study worth bringing to the attention of your oncologists if you're being treated with Paclitaxel or other taxane-based drug. Let's hope that the trial is replicated soon so that results are confirmed.

Anyone looking for the details should take a look at the (open access) paper reporting the result here:

Monday 6 August 2012

Fighting Cancer?

I've written before about the metaphor of a "war on cancer" - not a phrase I find particularly helpful. One aspect of this "war" is that patients are seen as in a personal battle with the disease. They are in a fight with cancer - the disease is at war with them - and the weapons in that war are toxic treatments like chemotherapy, radiation and radical surgery. I don't think these are useful images and are more likely to inspire horror than hope.

I am reminded of all this by reading a really interesting blog post from a person with Li Fraumeni Syndrome and who currently has a rare form of cancer called Leiomyosarcoma,. The blog is called 'Always Look On The Bright Side...' - and the post on 'Fighting Cancer - A Personal View' is well worth a read.

Thursday 19 July 2012

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...

Friday 13 July 2012

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.

Wednesday 4 July 2012

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:

Tuesday 19 June 2012

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.

Wednesday 23 May 2012

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:

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.

Wednesday 9 May 2012

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.

Monday 7 May 2012

BBC Catches Up With

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:

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.

Thursday 3 May 2012

Osteosarcoma outcomes getting worse

As regular readers will know, my son George died from metastatic osteosarcoma just over a year ago. What struck us at the time was the fact that there were no new treatments on this horizon - and that the obvious things to try (like zoledronate, ibandronate or other bisphosphonates) weren't being trialled despite them being used in palliative care for bone metastases in other cancers.

I've also written about the awful bone cancer statistics in the UK before. Now a new study (A Meta-Analysis of Osteosarcoma Outcomes in the Modern Medical Era,  Sarcoma, 2012) looks across the board at how osteosarcoma survival statistics have changed over the last thirty years. The findings are pretty grim:
Our study confirms suspicions regarding the lack of statistical improvement in osteosarcoma survival over the last thirty years. In fact, DFS (disease free survival) at the 3-year, 5-year, and 10-year marks have shown recent decreases over the last two decades. After steep improvements up until the 1970’s, overall survival at the 5 and 10-year marks has simply plateaued with lack of statistical improvements. Similarly, recurrence rates have fluctuated in the modern era, without significant improvement. This lack of improvement is also true in subset populations like pelvic metastatic cases, with actual decreases in survival in both of these populations over the last two decades, though these decreases did not reach statistical significance.
In other words not only have things not improved, they've gone backwards.  

This stinks. If the treatments haven't changed, then what explains the decreased survival? The drugs haven't changed, so what has? It can only be the formalisation of protocols and clinical practices.

Surely this is an issue that deserves some priority - including from anticancer activists and campaigners.

Wednesday 25 April 2012

George - One Year On

Loss. Such a small word to describe such a vast depth of sadness and heartache, but it's the word that best describes what we feel. It's so hard to believe that it is one year to the day that Georgie died. One year. We function now. We go to work, to school, engage with the world. But that sense of loss is with us always; an invisible cloak of sorrow that cannot be shed.

In that year we've made small steps to honour George's memory - such as setting up the TP53 Trust in his name - and have come to know other families with similar horrific histories. With time we hope we can make more progress, to make a real difference in the fight against this evil disease. It won't bring George back - the world will never regain its shape - but if we can help others to avoid the same loss, then perhaps it will make our loss easier to bear. George would have approved.

Thursday 19 April 2012

Is Mammography Screening Always A Good Idea?

I had, like most people, always assumed that mammography screening was a thoroughly good thing. If there was a controversy about, I had assumed it would be one that would come down to costs versus benefits. The assumption being that the only thing stopping mammography screening being rolled out to younger women was just about money. At no point had it ever occured to me that there might be scientific controversies associated with screening. That was until I found out about Peter Gotzsche and his argument that mammography screening was actively harming women. My first thought was that this must be about sloppy diagnosis - if women were being harmed it was because some of them are being misdiagnosed and then subjected to the array of harsh treatments - chemotherapy, radiotherapy and radical surgery. But no, his point is more subtle than that and comes down to basic oncology. His key finding, based on the data from randomised clinical trials, is that women are being over-diagnosed. And it wasn't until I read his book, Mammography Screening: Truth, Lies and Controversy (which I have reviewed here:, that I got the point.

In effect it boils down to a simple fact - not all breast cancers will grow, spread and ultimately kill the women who develop them. There are cancers that are slow-growing or which sprout, shrivel and die and which actually do not cause any health problems whatsoever. Many women will develop these types of tumours and never even know it. The problem is that we don't have any clear way of differentiating between these tumours and the ones that turn into killers. What screening does then is pick out all tumours - the safe and the dangerous. And because we don't know which is which doctors have no choice but to treat them all. It's not that women are being misdiagnosed, the tumours that are picked out are real, it's that some of those tumours are less dangerous than the treatments that follow.

Wednesday 18 April 2012

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:

Thursday 12 April 2012

Standards in Cancer Research

As regular readers of this blog will know, I believe that the relative lack of clinical success arising from cancer research is a major issue that demands attention from patients, patient advocates and the research community alike. In a recent post I pointed out that:

The truth is that there is an awful lot of money invested in cancer research - there are billions of dollars of funding from governments, private foundations, the drugs industry and members of the public donating to the cancer research charities. If it was just a matter of money the fight would have been won by now – or at least be further along than we currently are.

If it's not just a question of funding, then how can we explain why new treatments are so slow in coming? And why are the new treatments that do appear so often disappointing?

Interestingly enough a new article in the journal Nature (considered one of the world's leading scientific journals), casts an eye over the cancer research landscape and comes up with some depressing findings. What the authors find is that much pre-clinical research (i.e. research aimed at therapeutic outcomes rather than theoretical understanding) is pretty much a waste of time. While the papers may generate other papers and research (and gain the authors much prestige and funding), when it comes to reproducing the results in other laboratories or by other researchers there is nothing there. In fact a drug company, Amgen, attempted to reproduce the results from a number of 'landmark' cancer research papers and only manage to succeed in 11% of them.

Why is this? One of the reasons they highlight is similar to the one I have also discussed:

They include the use of small numbers of poorly characterized tumour cell lines that inadequately recapitulate human disease, an inability to capture the human tumour environment, a poor appreciation of pharmacokinetics and pharmacodynamics, and the use of problematic endpoints and testing strategies.

And, also echoing a point I have made previously on this blog:

What reasons underlie the publication of erroneous, selective or irreproducible data? The academic system and peer-review process tolerates and perhaps even inadvertently encourages such conduct. To obtain funding, a job, promotion or tenure, researchers need a strong publication record, often including a first-authored high-impact publication.

If this isn't a major scandal than what is? There are many anti-cancer activists now campaigning on trivia like plain packaging for tobacco when the real campaign needs to be focused on things like this. We should be demanding more from researchers, from academia and from the medical profession - not arguing over what colour wrapping we should have on cigarettes.

I'll leave the final words to C. Glenn Begley and Lee M. Ellis, authors of the article in Nature:

We in the field must remain focused on the purpose of cancer research: to improve the lives of patients. Success in our own careers should be a consequence of outstanding research that has an impact on patients.

Cancer researchers are funded by community taxes and by the hard work and philanthropic donations of advocates. More importantly, patients rely on us to embrace innovation, make advances and deliver new therapies that will improve their lives. Although hundreds of thousands of research papers are published annually, too few clinical successes have been produced given the public investment of significant financial resources.

Monday 26 March 2012

Opiates, cancer and naltrexone

An interesting paper in Anaesthesiology, (and yes, I know it’s not top of everyone’s reading list), looks at the influence of the mu opiod receptor (MOR) on cancer progression. While you may not have heard of the MOR, you will have heard of the drugs that target this receptor: morphine, fentanyl, heroin and other opiates. These are among the most widely used of pain-relief drugs in current medical practice. In particular these drugs are widely prescribed for cancer patients, either when undergoing surgery or when they are suffering from pain. The question of whether these drugs have an effect on cancer progression is one that is directly relevant to cancer patients here and now. While it has been known for some time that opiate drugs possibly have some indirect effects on disease progression because of the depressive effect on the immune system, the authors of this paper take things a step further and ask whether there is also a direct pro-tumour effect induced by these opiates.

The starting point for this new work is that the authors had worked with the drug methylnaltrexone (part of the same family of drugs as naltrexone), which blocks the operation of the MOR but which does not cross the blood/brain barrier. This means that while methylnaltrexone blocks the operation of opiate drugs, because it doesn’t cross into the brain it doesn’t interfere with the pain relief that opiates are used for. The clinical rationale for using methylnaltrexone is that it doesn’t stop the pain relief, but it does stop constipation and other side effects of opiates.

Wednesday 21 March 2012

Reverse Warburg Effect and Breast Cancer Biomarkers

I have written before about Michael Lisanti’s ‘reverse Warburg effect’ theory, and interviewed one of Lisanti’s collaborators in the UK, Dr Anthony Howell of the Christie Cancer Centre in Manchester. Briefly, the theory states that tumour cells ‘cannibalise’ surrounding tissues by creating highly oxidative conditions which force non-cancerous cells into metabolic states that produce nutrients that the tumour cells feed on. This is in contrast to the ‘classical’ Warburg theory, which states that it is the tumour cells which switch metabolic states.

This new theory radically over-turns the conventional view of tumour metabolism and makes a number of predictions which have direct clinical relevance. It also suggests that the traditional explanation of the Warburg effect is due in part to the in vitro models of cancer that have been used – in other words it’s due in part to scientists having the wrong models of cancer to play with. In the test tube isolated cancer cells do exhibit the ‘classical’ Warburg effect as they adapt to those conditions, but in real tumours the conditions are different and evolutionary pressures leads to this ‘reverse Warburg effect’.

While all of this might be of academic interest to the research scientist, does it have any relevance to the patient or the clinician? And the answer is that yes it does, in two distinct ways. The first is the new theory makes some specific predictions on how tumours behave and on how they interact with the surrounding tissues. In particular the theory suggests some new biomarkers that can be used to identify patients at high risk of early breast cancer recurrence, metastasis, drug and hormone resistance and decreased survival. Secondly, and linked to the first point, the new theory suggests some interesting new avenues to explore for treatment.

In a new paper, Lisanti and his team examined tumour samples from 180 triple negative breast cancer patients looking for specific markers related to his theory. The results of tissue analysis showed that having high levels of MCT4 (a marker of hypoxia, oxidative stress and aerobic glycolysis) in the tumour stroma (the cells that surround the tumour) was highly related to a decreased overall survival rate. This is a significant finding, being able to identify those patients at highest risk is vitally important.

Tuesday 13 March 2012

The Wrong Models of Cancer - Part 1

There is a commonly held belief that one of the primary reasons for such slow progress in the fight against cancer is financial. Without adequate funds, the story goes, scientists have not been able to make the positive moves towards new treatments that the ‘war on cancer’ has been promising for decades. The reality is, unfortunately, a lot more complicated. The truth is that there is an awful lot of money invested in cancer research – there are billions of dollars of funding from governments, private foundations, the drugs industry and members of the public donating to the cancer research charities. If it was just a matter of money the fight would have been won by now – or at least be further along than we currently are.

If it’s not just a question of funding, then how can we explain why new treatments are so slow in coming? And why are the new treatments that do appear so often disappointing?

One part of the answer, in my opinion, is that scientists have been focused on the wrong targets. As I have previously written, for example in the articles on How To Read A Cancer Paper, much early stage cancer research is done in vitro. Simply put, it means that researchers test new drugs in test tubes. Strictly speaking they’re not test tubes but flat dishes with a layer of growth medium (food and a nice environment for cells to grow on) on them. These flat dishes – often called Petri dishes – then have a layer of cancer cells grown on them. Mostly these cancer cells come from standardised cells lines that represent a particular type and sub-type of cancer – for example hormone resistant prostate carcinoma, or Her2+ breast cancer. While the distant ancestors of these cells will have come from patients, the cells supplied from the standard cell libraries have been grown in cultures from one generation to the next over many, many years. And this is one aspect of the problem.

Thursday 8 March 2012

Breast cancer and Li Fraumeni Syndrome

For women with Li Fraumeni Syndrome (LFS), the threat of breast cancer is ever present. The life time risk of developing breast cancer before the age of 60 is 49% for women with LFS. However, as with all cancers, there are many sub-types of breast cancer, some of them more amenable to treatment than others. So for this reason discovering whether there is a correlation between LFS and particular types of breast cancer is especially important. And the good news is that the picture that a positive picture is emerging from the studies being performed.

The latest paper looks at results from the breast tumour biopsies of 39 women with LFS (and while 39 looks like a low number, this represents the largest sample that has been examined so far). The average age at diagnosis of these women was 32. In all 43 tumours were examined, and of these 32 were found to be invasive ductal carcinomas and 11 were ductal carcinomas in situ (DCIS). Of the invasive tumours, 81% were high-grade, and 84% were hormonally dependent (i.e. positive for ER and/or PR). Additionally, 63% of them were positive for HER2/neu - as were 73% of the less dangerous DCIS tumours. Furthermore, 53% of the invasive tumours were positive for both ER and HER2.

What does this all mean?

It means that the majority of breast cancers in LFS patients are of the types that are more amenable to treatment. In the words of the original paper: 
These findings suggest that modern treatments may result in improved outcomes for women with LFS-associated breast cancer.
The trick now is to take these findings and look to see what it means in terms of chemoprevention. Are there protocols out there that can be adapted to reduce the risk of breast cancer in female LFS patients?

Tuesday 28 February 2012

Fasting and Chemotherapy

In a recent article on Low Carb Diets And Cancer, we looked at some interesting results of studies on low carb diets on established tumours. The conclusion to that study showed that a low carbohydrate, high protein diet:
...reduces blood glucose, insulin, and glycolysis, slows tumor growth, reduces tumor incidence, and works additively with existing therapies without weight loss or kidney failure. Such a diet, therefore, has the potential of being both a novel cancer prophylactic and treatment, warranting further investigation of its applicability in the clinic, especially in combination with existing therapies.
Well, you can’t get lower carb than not eating altogether, and that’s exactly what another new paper explores as an option. Published in the journal Science Translational Medicine, you get a clear idea of what it’s about from the title: Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell
Types to Chemotherapy
. As with the previous paper, much of the data in this paper comes from mice models of cancer. So, as always it’s important to keep in mind that what works in mice doesn’t necessarily work in humans. Aside from anything else, mice don’t have to cope with the stress of knowing they have cancer…

February 29th is Rare Disease Day 2012

In the words of the the Rare Disease UK network:

  • 1 in 17 people will be affected by a rare disease at some point in their life.
  • This amounts to approximately 3.5 million people in the UK.
  • 75% of rare diseases affect children and 30% of rare disease patients will die before their 5th birthday.
  • There are over 6,000 recognised rare diseases.
  • Collectively rare diseases are not rare.
Rare Disease UK (RDUK) is the national alliance for people with rare diseases and all who support them. We believe that everyone living with a rare disease should be able to receive high quality services, treatment and support.
One of those rare diseases is Li Fraumeni Syndrome, and the George Pantiarka TP53 Trust is proud to announce that it has joined RDUK. To find out more about the network, and what it's doing for Rare Disease Day 2012 please take a look at:

In particular note that there's a political angle to this campaign:

It has now been over 2 years and 9 months since the Government signed the European Recommendation which committed them to developing a plan for rare diseases.
It has been a year since Rare Disease UK launched our comprehensive recommendations to inform the plan in our report Improving Lives, Optimising Resources: A Vision for the UK Rare Disease Strategy

As a result, we are using Rare Disease Day to call for no further delays to the plan. Please help us to do this by writing to your politician! If you have done so already, thank you very much – we have had a fantastic response rate! RDUK has also been busy contacting politicians, but as their constituent, you have the most influence over your representatives.

Information on how to contact your local politician and template letters depending on whether you live in England, Scotland, Wales or Northern Ireland are available here.

Let's hope that the activity and extra focus on February 29th has an effect at last.

Monday 27 February 2012

LDN Research Trust Newsletter

The February 2012 newsletter of the LDN Research Trust is now available here:

As well as covering all the news from the world of Low Dose Naltrexone research, there's also an article about this website and the work of the George Pantziarka TP53 Trust. It's a good read - so if you're at all interested in low dose naltrexone it's definitely worth following up.

Monday 20 February 2012

George Pantziarka TP53 Trust On Facebook

As part of our strategy to make contact with as many people as possible with Li Fraumeni Syndrome and other TP53-related conditions, we have just created a George Pantziarka TP53 Trust presence on Facebook. As well as a Facebook page here:, there is also a group here:

If you're on Facebook please drop by. If you know of anyone with a TP53-related condition, or an interest in TP53, then please pass on the word.

Monday 13 February 2012

Interview With Galina Selivanova

Professor Galina Selivanova (GS) heads a research group in the Department of Microbiology, Tumor and Cell Biology of the Karolinska Institute in Stockholm, one of Europe's leading medical schools and research institutes. Her work focuses on re-activating TP53 using small molecule drugs, some of which are beginning to emerge into clinical trials. She is generally acknowledged to be one of the world's leading researchers on TP53 as a medical target in oncology. She is interviewed here: and what she has to say is generally optimistic, which is welcome given how optimism is in precious short supply when it comes to Li Fraumeni Syndrome

Friday 10 February 2012

Oncology Nurses Society On LFS

General information on Li Fraumeni Syndrome is comparatively rare, which is frustrating when you're trying to explain what it is to a doctor, nurse or other medical profession, let alone family and friends. However, the journal ONS Connect, published by the Oncology Nursing Society, have published a five-minute introduction to Li Fraumeni Syndrome.

Obviously aimed at the oncology nurse, it covers a reasonable level of detail and describes the current state of the art when it comes to the condition. If you need to point your nurse or doctor to a source that they can trust, then point them at this article:

And of course, point them to as well...

Monday 6 February 2012

Omega 3s, Stress and Cancer

Stress is a fact of life for cancer sufferers not just when they are undergoing treatment, but beyond that too, once they are in remission. It’s a fact life for people with Li Fraumeni Syndrome and other TP53-related conditions, and for those with Lynch Syndrome or other inherited conditions that predispose to cancer. This would be bad enough if we didn’t also know that stress can negatively affect the health, including negatively affecting the immune system. And, to cap it all, this knowledge itself causes stress, thereby creating one of those horrible vicious cycles that can lead to depression and anxiety.

Before reaching for the anti-depressants though, there are some positive things that can be done to tackle this stress. And, as a bonus, many of these steps to tackle stress can also boost the immune system and generally have a positive effect on health. What’s more, there is also accumulating evidence that many of the steps that I will outline are also good for people in the middle of cancer treatment, not just those who are in remission or worried about the next test results.

These positive steps include:

  • Exercise
  • Meditation
  • Tackling sleep problems
  • Improving diet
  • Omega 3 fatty acids

Tuesday 31 January 2012

Bisphosphonates and side effects

It's generally accepted that bone tumours - whether from primary tumours like osteosarcoma or from metastatic disease - are hard to deal with. Bone cancer pain is difficult to control, and bone tumours can cause fractures and other significant problems, so finding a way of controlling these tumours is essential. To this end there is a whole class of drugs called bisphophonates which are emerging into general oncological practice. These drugs have been found to be effective in slowing the spread of bone tumours, and in helping deal with the pain that they induce. In terms of primary bone cancers, a number of trials are on-going in which these bisphophonate drugs are being used alongside the standard treatments for osteosarcoma. And, as an added bonus, there is evidence that the newer bisphosphonates such as zoledronate and ibandronate, have direct anti-tumour and immune-boosting effects too.

However, there is a big risk that comes with these drugs, which originated as treatments for osteoporosis, and that is a condition called osteonecrosis of the jaw (ONJ). This condition, which occurs in a small subset of patients can cause severe lesions in the jaw, and which can, in a very few cases lead to the crumbling of the jaw. To date there has been no way of knowing which patients are likely to get ONJ, which is a worry for patients taking them, and of course a concern for doctors who prescribe them.

But there may be some good news on the way. Researchers at the Columbia University College of Dental Medicine have done an analysis of patients who developed ONJ, looking at whether or not there is a genetic component to it. And it does appear that this is the case, with variations in a gene called RBMS3 being associated with the occurence of ONJ. This means that in time a genetic test will become available which will help doctors predict which patients are more or less likely to develop ONJ. If it means that doctors will become more confident in prescribing bisphosphonates to cancer patients who need it, then that's really good news.

For more details see the paper here:

Monday 30 January 2012

Li Fraumeni Syndrome - New Surveillance Protocol

Many people who have Li Fraumeni Syndrome (LFS) or other TP53 abnormality are often diagnosed when they are suffering cancer - sometimes for the second or third time, as happened with our son George. They are in the thick of cancer treatment and are focused on the immediate problems at hand. However, for people who are not suffering from cancer, a diagnosis of LFS or other TP53 abnormality is likely to be a huge shock. All of a sudden the future becomes uncertain and frightening. The stress is immense.

The answer to the obvious question of 'what happens now?', is most often a variation on 'wait and see'. Currently, in the UK at least, the key thing is to put in place a system in which any LFS patient gets high priority should symptoms crop up. No waiting around for appointments for investigations, no hanging around while one doctor after another mulls things over.

However, a team of doctors in Canada and the United States have trialled a more active program of clinical surveillance. This program consists of regular blood tests and scans, trying to catch things before they become symptomatic. This is a major step forward for LFS patients.

I have written about it on the George Pantziarka TP53 Trust website here:

It's required reading for anyone interested in TP53 and Li Fraumeni Syndrome. If you are a sufferer it's something you really need to know about, and, just as importantly, it's something that your doctors need to know about too.

Wednesday 18 January 2012

No To The US Research Works Act

Access to information is essential to patients and doctors researching different medical conditions, including cancer. Journal papers offer the latest thinking on disease progression, reports of investigations in fundamental biology, new drugs, clinical trial results and so on. For those with chronic or life-threatening conditions, medical research offers the hope of new insights, new treatments and greater understanding. And, as I’ve written before on this site, access to medical research should be free to all, especially for the research that we – as citizens – have paid for through our taxes.

However, free and open access, as enshrined in the policies of the National Institutes of Health in the United States, conflicts with the commercial interests of the journal publishers. These companies make a lot of money by publishing scientific journal. The subscription fees for journals run into the thousands of dollars a year – way beyond what we as patients and their carers can afford. But the journals make money because university and medical school libraries, private companies and so on subscribe to them. An increased move to open access threatens this source of income.

So, the journals are fighting back and in the US there is now a Research Works Act being considered. This would basically take the publicly funded research results that are published by the NIH and open access journals back behind a paywall. No more free access to the latest information. If you want a particular paper you’ll either have to gain access to a university library or else pay the fees to access the paper (and fees range upwards of $30 per article).

If this Act goes ahead it will be a real loss. It will also be a grave injustice. For tax payers it will mean they are paying twice – once for the research to be carried out, and again should they want to read the results for themselves. But it will also mean denying access to potentially life-saving research to cancer patients at a time when they need it the most.

This site gets a lot of traffic from the United States. Please, if you are a US citizen please act now to stop the Research Works Act from becoming law. Write to your representative, write to your local newspaper, and if you are a scientist or doctor then please write to your professional association or society to take a stand in defence of patient rights.

Tuesday 10 January 2012

An Invaluable Service by Irene Pantziarka

When entering the unknown world of watching your child slip slowly on to the path that leads towards death and the finality of non-existence, there is little comfort to be found, particularly if you are an atheist. Consequently, any support that can be identified, which enables you to go on and face each day, making the most of every moment that your son or daughter is still with you, becomes a lifeline. 

For our family, such support came in the form of the paediatric outreach nursing team (PONT) from our local hospital (Kingston). This is a team of nurses who, as the title suggests, visit families in the community, providing certain nursing services for sick children. This means that families do not have to journey to hospital every time they need for example a dressing changed or a line flushed. The nurses work around the family’s schedule. They disrupt family routine as little as possible, fitting in with your convenience, rather than expecting you to fit in with theirs. This is in great contrast to the experience of being in hospital, where almost everything seems to be done at the hospital’s convenience and patients can wait endlessly, with no apology given. In other words, the PONT service is family-centred and providers of other hospital services could learn a huge amount from them. 

I cannot stress enough the value of this service to families like ours. The PONT figured in our lives from the beginning of George’s treatment – changing dressings, flushing lines, offering help and advice – but it was during the final stages of our son’s cancer that their presence became invaluable.