Lansoprazole and resistance to chemotherapy

For this first post of 2012 I want to start on a positive note by highlighting an interesting and relevant piece of research from Italy. Chemoresistance is the term used to describe the process whereby cancer cells become resistant to chemotherapy. Unfortunately this is a serious and widespread problem, right across the spectrum of cancer types. Tumours that regress quickly from the initial rounds of chemo, sometimes shrinking away to nothing almost, suddenly seem to bounce back, growing again and shrugging off repeated rounds of the chemo that seemed to knock them out. In many cases these resistant cancer cells become ‘multi-drug resistant’, which means that second and third line chemotherapy treatments also have little or no effect. So, finding a way of reversing this resistance is an important aim in cancer research, and one which is clinically relevant across most kinds of cancer.

It’s this problem that a team of researchers and clinicians in Italy have tackled in a clinical trial. Building on work previously done in the laboratory, Stefano Fais and his co-workers carried out a clinical trial on cats and dogs (now called ‘companion animals’ rather than pets!) with cancers that were resistant to standard chemotherapy. Don’t for one minute think that because the patients were animals that this is not relevant research. Cancers in cats and dogs are much closer to human cancers than cancers in rats and mice. In some types of disease, such as osteosarcoma, the disease acts in exactly the same way that it does in people, and is treated with the same drugs and treatments.

These animals were treated with the common anti-acid drug lansoprazole at high doses – a drug that is available over the counter in the UK – along with the chemotherapy drugs that often fail due to the development of chemoresistance. The response of these animals was compared to another set of animals that had the conventional chemo-only treatment (it was the owners of the animals who decided to stick to the conventional treatments only).

The results were very clear. In the lansoprazole treated group, more than two thirds of animals showed partial or complete responses, compared to 17%of animals in the chemo-only group who showed short-lived partial responses. What’s more, even in the non-responders in the lansoprazole group, the owners of the animals indicated that their pets showed improved quality of life – less pain, less weight loss, greater agility etc.

Coley's Toxins In The UK

Coley's Toxins is an cancer therapy from the pre-history of modern oncology. Developed by surgeon William Coley at the end of the 19th century, this was a treatment that showed some impressive results against a range of hard to treat cancers - especially sarcomas. Coley began the treatment after noticing that some patients with cancer experienced tumour regression after becoming infected in hospital. These rare cases of spontaneous remission were regarded as miracles, which they still are, pretty much. The infected patients would develop severe fevers, chills, aches and pains and the rest of the signs of a massive immune response that ended with the tumours being attacked by the immune system.

Coley took this idea forward and developed a treatment that consisted in inducing this severe immune response by injecting bacterial material into his patients. The patients reacted to this injection of 'bacterial toxins' by developing the feverish response as their immune systems kicked in. And, in some cases, the resulting immune response did indeed lead to the tumours being attacked and ultimately disappearing. This did not happen in all patients, but it happened at a rate that is comparable to some of the more modern cancer treatments. And, it must be said, because the tumours were cleared by the immune system, there were none of the long-term side-effects you get from chemotherapy or radiotherapy, and in many of those individuals where the tumours disappeared the treatment really did lead to a cure.

However, with the advent of radiotherapy, chemotherapy and advances in surgery, Coley's treatment fell by the way-side. Coley is often credited with being the 'grandfather' of cancer immunotherapy, but largely his treatment barely exists as a historical footnote in oncology. There is still a fair degree of interest in it from those interested in alternatives, but in the mainstream of medicine Coley's toxins are dead.

Curcumin Trial In The UK

One of the nice things about the ClinicalTrials.gov website, (which I have discussed previously here: http://www.anticancer.org.uk/2011/08/searching-for-clinical-trials.html), is that it lets you set up RSS feeds based on yor own search criteria. It's through this mechanism that I've learned about a new clinical trial for cancer using curcumin. What's more, this new trial is based in the UK, which is welcome since most curcumin trials have been in the US and other countries.

As with many of the current trials of curcumin, this one uses it as an adjunct to conventional chemotherapy. Specifically this is a trial aimed at patients with inoperable colorectal liver metastases who will be commencing standard oxaliplatin-based (FOLFOX) chemotherapy, In addition to their normal chemotherapy, patients will be given oral curcumin tablets (curcumin C3 complex, to be exact). In the first phase of the trial the aim is to test the safety and tolerability of curcumin and FOLFOX, with doses of up to 4g per day of curcumin. In the second phase of the trial patients will be randomised and some will received FOLFOX and curcumin, and some will just have the standard FOLFOX treatment.

In many respects this trial is treading familiar ground - curcumin has been trialled as an adjunct to other chemotherapy treatments for other cancers. One example that springs to mind are the trials of curcumin and gemcitabine for advanced pancreatic cancer. In one such trial 4g doses of curcumin were tried, but patients found it hard to take the volume of tablets, in another trial patients took up to 8g of curcumin without problem.

While there's a lot of excitement about curcumin as a cancer treatment, it's fairly clear by now that it is not a viable therapy on its own as things stand. The future of curcumin as a cancer treatment lies in two directions. The first as a support to existing treatments - which is what this trial is looking at. Curcumin may blunt some of the side effects of chemotherapy and radiotherapy, may make these treatments work better and may reverse drug resistance in some tumours.

The other path for curcumin lies in new formulations. This is an area of intense activity at the moment. In some cases scientists are working to improve the bioavailability of curcumin through using liposomes or other technologies. These new formulations take curcumin and simply make it more available to the body, particularly to tumour cells. A different approach is to take curcumin as a starting point and to alter the chemical structure to create new drugs that are based on it. These new drugs are more potent than curcumin and the hope is that they will be more powerful anti-cancer agents.

Both these approaches have merit, but for now it's good to see that curcumin is being tried in trials now.

To find out more about this this trial take a look here: http://clinicaltrials.gov/ct2/show/NCT01490996

Comment Spam

One of the things I've discovered since starting this blog, is that there are some people for whom no website, forum or blog cannot be exploited for gain. This site encourages comments from readers, but it has to be said that there aren't many comments being published. It's a shame, but I guess that some people just want to read and not write. The fact that traffic is increasing and that many of the visitors are being referred here via other blogs, Facebook and other social media is positive.
 
But comments are being left here that I'm not publishing.

This site uses comment moderation - comments have to be approved before being published - and it's a good thing too. Everyday there are comments left here which are really just 'comment spam'. The comments contain some innocuous are often barely literate text - 'this is a good useful nice site, for sharing' - along with a link to another site. Usually the link leads to some company selling something cancer-related: supplements, nursing care, clinics etc.

I think it's really low to try and exploit an anti-cancer site like this - have these people got no conscience?

The George Pantziarka TP53 Trust

TP53 is a gene that functions as a tumour suppressor. One of its jobs is to create the p53 protein, which acts to kill cells that have become cancerous. When the TP53 gene goes wrong, it means the body loses one of the key mechanisms it has for stopping damaged cells becoming cancers. Many people who develop cancer end up having the TP53 gene damaged in their tumours, but it functions normally in the rest of their body. However, there are some people who are born with a damaged TP53 gene, and for these people the risk of getting cancer is incredibly high. In many of these cases the damaged TP53 gene is inherited - it is passed down from parent to child.

Li Fraumeni Syndrome (LFS) is one of the most serious forms of inherited TP53 disorder. My son, George, had LFS, which we assume he inherited from his mother, who died of ovarian cancer at the age of 29, when George was just over a year old. As I have written before, we did not know that George had LFS until after he was diagnosed with his third cancer - the osteosarcoma which ultimately killed him.

While LFS and other congenital TP53 disorders are rare, the fact remains that there is little awareness of the issue, both amongst the general population and also amongst the medical profession. There are no support groups, no charities, no central information resources and currently no central registry of sufferers. For those families with LFS or other TP53 disorders, it can be a lonely and frightening existence, with children and adults alike succumbing to one or more cancers.

Having discussed the issue with a number of doctors and researchers, we have decided to create the George Pantziarka TP53 Trust, in George's memory. The aim is to provide support to families and individuals, to provide information to all, and to help foster understanding and research into the condition.

As a first step we will be launching a web-site and forum in the new year. The plan is to use the site to bring together all those affected or interested in the condition. Further down the line we hope to register the Trust as a charity so that we can expand the range of activities that we can undertake.

For now, any offers of support would be greatly appreciated.

Open Access To Research

Regular readers of this blog will be aware that I spend a lot of time reading and reviewing the research literature on cancer. I see translating that research into plainer language that is more accessible to the average person is one of the things that this site can usefully do. As such having access to the research papers is essential. Unfortunately getting hold of papers is not always an easy task. Science journals are incredibly expensive to subscribe to (typically many hundreds of pounds a year) and there are a lot of them. The whole system is geared towards providing access to research to academics and researcher (mostly) via university or institutional libraries. Without this library access an individual can buy a copy of a specific paper - but here the cost ranges from a few tens of pounds to over a hundred. For most people this is prohibitive, especially if you are a cancer patient or carer and are doing a lot of reading.

The thing is, a lot of that research is publicly funded. We pay for it through our taxes - indirectly, of course, in the form of research grants and so on. So, as members of the public we pay for the research but we can't always get to read the results of that research. However you look at it, this is a really poor state of affairs, particularly when it comes to medical research.

It's not all bad. There are an increasing number of journals which are published on an open access basis. In other words the journals publish their work online and for free. Some journals, such as BMC Cancer, are well-established now, and publish high quality work that can be downloaded by anybody. In other cases journals make older articles available for free, so that for the first six months or a year a paper must be paid for, but after that it's free. Another option that some journals have adopted is to make selected articles free - which is good if it's one that you're looking for but rubbish if not. Finally, there are also some journals who allow access to articles by patients for free, but everyone else has to pay. Normally this involves filling in an online form to gain access to the article.

Cancer and lifestyle choices

The headlines are startling: over 40% of cancers are down to lifestyle. The opening paragraph of the BBC News report states it bluntly:

Nearly half of cancers diagnosed in the UK each year - over 130,000 in total - are caused by avoidable life choices including smoking, drinking and eating the wrong things, a review reveals.

For those with cancer, or who have family or friends suffering from the disease, this makes for grim reading. Because, like it or not, there's a moralistic sub-text here: in over 40% of cases, cancer is the fault of the patient. If only they'd chosen the right life-style, they wouldn't be sick.

Now, that isn't what the articles say, but it's a clear implication. Before we go any further though, perhaps we ought to back up a little and ask what the science really says...

Firstly, we have to be clear that what we're talking about here are projections based on a series of mathematical models. These projections take a series of risk factors - say smoking or alcohol consumption - and then compare the increased risks of developing cancer based on comparing current consumption levels and what are considered the 'optimum' levels. So, for example, you take the additional risk of developing cancer per unit of alcohol, the difference between current consumption and the ideal level and calculate the increased risk. Now take that increased risk and multiply by population and you get your projected number of cancer patients. It's a bit more complicated than that, of course, but in principle that's how it works. Add an additional set of factors for different types of cancer, and you've got a cascade of different variables that make up that final scary number.

So, all of this is subject to many different assumptions about risk factors, current consumption levels, ideal consumption levels, population growth etc.