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Tuesday 31 May 2011

New clues to how humble painkiller stifles cancer growth

reposted from: https://msds.open.ac.uk/students/course.aspx?c=S807_2011B
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Thursday 26 May 2011

Cancer Research UK Press Release

CANCER RESEARCH UK scientists have shed light on how a common class of painkillers – which includes ibuprofen – may interact with a key protein that fuels the growth of many different types of cancer, according to a study published in the journal Chemical Communications today (Thursday).
Ibuprofen is one of several profens - a particular group of non-steroidal anti-inflammatory drugs (NSAIDs) - being investigated for their ability to prevent cancer.
The University of Bath research team* carried out an analysis of drugs in the same class as ibuprofen and discovered that they are all processed by the body in exactly the same way – through a protein called AMACR, which converts the drug into its active form.
AMACR is overactive in almost all prostate cancers, some bowel cancers and several other types of cancer and is thought to fuel the growth of the disease by boosting the cell’s energy supply.
So understanding how drugs like ibuprofen might alter AMACR activity could help scientists better understand how they are able to block cancer growth.
Lead author Dr Matthew Lloyd, said: “Our study is the first to test other drugs in the same family as ibuprofen systematically and show that they‘re all processed by the same protein in the body. Some early laboratory studies have suggested that high doses of ibuprofen can halt the growth of prostate cancer cells, but the reasons for this aren’t well understood.
“Understanding more about how this protein is acting in cells and what molecules it interacts with could provide important clues to how this process works, hopefully opening up new avenues of research for treating prostate cancer in the future.”
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “This research is part of an international effort to understand how drugs like ibuprofen could prevent, or slow down, the development of cancer. But there are risks as well as benefits and long term use of these drugs can have side effects, such as bleeding and stomach ulcers. Understanding more about how these drugs work on a molecular level is a crucial step in being able to develop better targeted drugs with fewer side effects in future.”
ENDS
For media enquiries please contact the Cancer Research UK press office on 020 3469 8300 or, out-of-hours, the duty press officer on 07050 264 059.

References

Woodman et al., Chiral inversion of 2-arylpropional-CoA esters by human alpha-methyylacyl-CoA racemase 1A (P504S) – a potential mechanism for the anti-cancer effects of ibuprofen (2011), Chemical Communications, DOI: 10.1039/ClCC10763A.

Thursday 26 May 2011

Dichloracetate DCA links

reposted from:
http://www.nature.com/news/2010/100512/full/news.2010.236.html#B2
http://www.newscientist.com/blogs/shortsharpscience/2011/05/cure-for-cancer-resurfaces-and.html
http://www.newscientist.com/article/dn10971
http://en.wikipedia.org/wiki/Dichloroacetic_acid
http://en.wikipedia.org/wiki/Talk:Dichloroacetic_acid
http://scienceblogs.com/insolence/2010/05/dichloroacetate_dca_and_cancer_deja_vu_a.php
http://www.dca.med.ualberta.ca/Home/Media/articles.cfm
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Potential cancer drug DCA tested in early trials

reposted from: Cancer Research UK comments: http://scienceblog.cancerresearchuk.org/2010/05/12/potential-cancer-drug-dca-tested-in-early-trials/
crabsallover highlightskey pointscomments / links.

I read about DCA in Cancer Research UK newsfeed on 16th May 2011. It was also mentioned by Guy 
http://www.meetup.com/HASSNERS/messages/boards/thread/11130311/20#42889221 on 25th May 2011.

Update, 16th May 2011: Several websites are reporting that last week ‘cancer was cured without anyone reporting on it’. This is not true and seems, we think, to have arisen from a misreading of the date on the most recent paper on DCA (which was published on May 12th 2010 – i.e. this time last year).

Everything we wrote in the post and comments below stands – DCA is still only a ‘potential’ cancer treatment, and more research is needed to find out whether it’s safer or more effective than existing therapies.
- Henry

A bottle of tablets
DCA has been tested in a small trial
The controversial drug DCA (dichloroacetate) is in the headlines again, after researchers in Canada carried out a small-scale clinical trial of the drug in five patients with advanced brain tumours.
Over the past year or two there have been several articles in the news and on the internet about DCA, which was claimed to be cheap, safe and “kill most cancers”.

Understandably this  caused a great deal of interest, especially as DCA is an off-patent drug and appears to be non-toxic to humans (although it can cause significant side effects, as we’ll see later).
But before we jump to conclusions and hail DCA as a ‘wonder drug’, we need to look at the science behind the headlines.
What is DCA and how does it work?
A mitochondrion
Mitochondria are the 'power stations' in our cells
All our cells need energy to grow and function, including cancer cells. Simply put, our cells usually generate energy by breaking down sugar (glucose). To do this, they use a process known as the Krebs cycle, which takes place in tiny structures within the cell called mitochondria (the ‘power stations’ of the cell).

But cancer cells bypass this cycle and produce energy using a simpler process, known as glycolysis, which takes place outside the mitochondria in the cell’s cytoplasm (the main part of the cell).
Mitochondria play a crucial role in cells. As well as generating energy for the cell, they can also trigger the cell to die if it is faulty – a process that helps stop cancers from forming in the first place. 

Because cancer cells seem to switch off their mitochondria, scientists think this is one way in which cancer cells are able to evade death and remain immortal.

DCA, or dichloroacetate, is a very simple chemical and is similar to some of the chemicals involved in the Krebs cycle. In 2007,  researchers at the University of Alberta (led by Evangelos Michelakis) found that adding DCA to cancer cells grown in the lab kick-starts the Krebs cycle, turning the mitochondria back on again. This caused the cancer cells to stop multiplying and die. The team discovered that DCA didn’t affect healthy cells, because their mitochondria were functioning normally.
DCA has been tested as a treatment for children and adults with certain rare metabolic disorders.  This means that, at the doses needed to treat these diseases at least, DCA has been through clinical trials aimed at assessing its safety. Based on their results, the researchers have proposed that DCA could also be useful in treating cancer.
To begin to investigate if this is indeed the case, Michelakis and his team started by carrying out experiments on cancer cells grown in the lab. The team also studied rats that had been injected with cancer cells. They found that DCA could slow the growth of the rats’ tumours, and reduce their size. This did not prove that the cancers were completely cured, or that DCA could prevent cancers from growing.

It is important to stress that DCA had not then been tested as a cancer treatment in humans, despite the implication in news headlines that it “kills most cancers”. There are many research papers produced by scientists around the world every year that reveal potential new treatments for cancer. But it is important that every discovery is carefully investigated to make sure that it is effective and safe for use in patients, and DCA is no exception.
The University of Alberta researchers received approval for a human cancer trial in September 2007, involving 50 patients.  Now they have published the first results from five of those patients in the journal Science Translational Medicine.

The new trial
In this study, Michelakis and his team gave DCA to five patients with advanced glioblastoma, a type of brain tumour, in combination with surgery, radiotherapy and a drug called temozolomide.  It’s important to point out that the aim of this study was not to find out whether DCA could treat glioblastoma, but to figure out the safest dose to use for cancer patients. We already know that the drug can be safely given to humans – although it can cause side effects – but this is the first time it has been tested in people with cancer.
The study shed light on the dose that could be given to patients without causing nerve problems or other serious side effects.  Four patients were still alive after 18 months, and three showed some shrinkage of their tumour, but it is impossible to tell with such a small study whether this is longer than might be expected. And, given that they were also receiving other treatment, it’s hard to know if it was due to DCA at all.
As well as this small trial, the researchers also looked at the effect of DCA on tumour samples from 49 other glioblastoma patients.  They found that DCA could switch mitochondria back on in the cancer cells, although – crucially – it’s still not clear exactly how it’s doing this.
Finally, the team looked at tumour samples taken from the five patients on the trial, both before and after treatment with DCA, and found that the drug was again helping to switch mitochondria on. They also discovered other differences in the cancer cells’ metabolism before and after treatment.
A key gap in this trial is that, as we’ve mentioned above,  it’s not clear exactly how DCA is working. The researchers suggest that the drug may target cancer stem cells and prevent the growth of blood vessels into tumour, although they didn’t actually prove this.
Is it safe?
These results show that lower doses of DCA could, at least in theory, be given to cancer patients while avoiding some of the damaging side effects seen at higher doses. For example, a clinical trial of DCA for a childhood disease found that the drug caused significant side effects, affecting the nervous system. It is also known to be an environmental pollutant. And researchers have found that DCA can actually cause cancer in animals.
This is not necessarily a barrier to the use of DCA as a treatment for cancer – there are a number of powerful cancer drugs that are carcinogens themselves. And this is why we need to test them in clinical trials (as Michelakis and his team have begun to do here) to discover how they can be safely used to treat patients while minimising any harmful effects.
Why can’t we use it now?
It is understandable that people with cancer will want to try everything possible to help treat their disease. However, there is still no evidence – yet – to support the immediate use of DCA to treat cancer patients.
The trial in Canada is being conducted under stringent conditions both to ensure the validity of the results and to protect the participants from any unforeseen effects. Further clinical trials of DCA using more patients will help determine whether the treatment is more effective than the cancer therapies that are currently available.
There are reports that people are buying personal supplies of DCA from sources such as the internet. Cancer Research UK would strongly advise against this, as DCA still has not been shown to actually treat tumours successfully in patients. And it may be harmful when given to cancer patients without accurate dosing and medical supervision.
What will happen in the future?
It is clear that DCA is an intriguing drug – one of many currently being investigated by scientists around the world. It will be interesting to see the results of more extensive lab-based experiments and larger clinical trials of DCA. And cancer cell metabolism is certainly a productive area of research that we’re actively funding.
The fact that DCA is off-patent is no barrier to its development as a treatment for cancer. For example, Cancer Research UK has secured a licence for an off-patent drug called fenretinide, which could be used to treat rare childhood cancers. 

And there is certainly no “conspiracy” by pharmaceutical companies to prevent research into DCA – there is just not enough evidence at the moment to support its widespread use to treat patients.

While these results are intriguing, it is unlikely that this one compound represents “the cure” for cancer – and it is also unlikely that DCA is the “wonder drug” that the headlines portray. Cancer is a complex and multi-faceted disease, and it can be caused by a range of different faults within the cell. It is unlikely that any single drug could ever treat all forms of the disease.
There are many promising new treatments for cancer currently in development, funded by organisations across the globe – including Cancer Research UK.   If anything, these new results show why research is so important in bringing safe and effective treatments to people with cancer – they don’t provide definitive answers, but they support further investigations which may yield benefits for patients in the future.
Kat
Further reading:

References:
P. Kaufmann, K. Engelstad, Y. Wei, S. Jhung, M. C. Sano, D. C. Shungu, W. S. Millar, X. Hong, C. L. Gooch, X. Mao, J. M. Pascual, M. Hirano, P. W. Stacpoole, S. DiMauro, D. C. De Vivo (2006). Dichloroacetate causes toxic neuropathy in MELAS Neurology, 66, 324-330
Michelakis ED, et al (2010). Metabolic modulation of glioblastoma with dichloroacetate. Science translational medicine, 2 (31) PMID: 20463368
S BONNET, S ARCHER, J ALLALUNISTURNER, A HAROMY, C BEAULIEU, R THOMPSON, C LEE, G LOPASCHUK, L PUTTAGUNTA, S BONNET (2007). A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth Cancer Cell, 11 (1), 37-51 DOI: 10.1016/j.ccr.2006.10.020

Wednesday 25 May 2011

Open University, S807, Molecules in Medicine MSc.

February 2011 - I've started a 3 year part-time MSc in Science.

First year study: Open University, S807, Molecules in Medicine.

Conference reviews cancer prevention benefits of prophylactic aspirin

reposted from: http://www.alphagalileo.org/ViewItem.aspx?ItemId=103955&CultureCode=en via Google 'aspirin', 'cancer' alert
crabsallover highlightskey pointscomments / links.


Conference reviews cancer prevention benefits of prophylactic aspirin


In the report Gareth Morgan, from Older People’s Services, NHS Wales, outlined the current evidence on aspirin and cancer prevention;  while Peter Rothwell, from Oxford University, explored the effects of aspirin on colon cancer risk; and Sir John Burn, from Newcastle University, looked at aspirin in the prevention and treatment of hereditary colorectal cancer.
Based its safety profile aspirin is the chemoprevention agent of choice in colorectal cancer, said Dion Morton from the University of Birmingham. The fact that aspirin reduces the risk of colorectal cancer with a latency of 10 years indicates that adenoma prevention, rather than down-staging cancer or preventing progression is probably the mechanism involved. He proposed a trial in which patients with high risk adenoma should be randomised to adjunctive treatment with aspirin or placebo.
Jack Cuzick, from Cancer Research UK, said that the cost of Phase II studies for early validation of the role of aspirin in cancer prevention could be minimised by the use of biomarkers and precursor lesions as end points.
Gordon McVie, from the European Institute of Oncology, Italy, said that several issues remain unresolved including the dose-response relationship in the prevention of colorectal cancer and the effect of enteric coating. The combinations of aspirin with other treatments, he added, was an avenue worth exploring in clinical trials.
Concluding the conference chairman, Peter Elwood, from the University of Cardiff, said that evidence of the risks and benefits of taking aspirin should be presented to the public in a package of measures to preserve health to allow them to make informed choices.

Thursday 19 May 2011

Aspirin in the prevention of cancer

reposted from: http://www.lancet.com/journals/lancet/article/PIIS0140-6736(11)60669-7/fulltext
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The Lancet, Volume 377, Issue 9778, Page 1651, 14 May 2011
doi:10.1016/S0140-6736(11)60669-7Cite or Link Using DOI

Aspirin in the prevention of cancer

That aspirin can help to prevent cancer1 has caught the public's attention. How does this benefit compare with the rather modest benefit in lessening cardiovascular events previously reported in those at low cardiovascular risk? In a previous study of such patients,2 the prevention was only three events in women and four in men among 1000 people studied over 6·4 years. The cost was 2·5 major bleeds per 1000 per 5 years in women and three in men, so the overall benefit was truly modest. By contrast, the cancer prevention rates in the study by Rothwell and colleagues1 included 15 gastrointestinal cancer deaths per 1000 people over 5 years. These benefits vastly outweighed the risk of major bleeds.
In view of these new facts, we should no longer be reserved about recommending aspirin even for those at low cardiovascular risk. However, we are still lacking firm data on when aspirin should be started in those at low risk, and at which dose. The doses of aspirin protecting from cancer in Peter Rothwell and colleagues' study1 were in the range of 75—300 mg daily. My guess is to start at a low dose—say 75 mg—in the early 50s.
I delare that I have no conflicts of interest.

References

1 Rothwell PMFowkes FGBelch JFOgawa HWarlow CPMeade TWEffect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trialsLancet 201137731-41Summary | Full Text | PDF(502KB) |CrossRef | PubMed
2 Berger JSRoncaglioni MCAvanzini FPangrazzi ITognoni GBrown DLAspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trialsJAMA 2006295306-313CrossRef |PubMed
a Hatter Cardiovascular Research Institute, University of Cape Town Medical School, Observatory, Cape Town 7925, South Africa

Friday 6 May 2011

Call for all to take statins after 55

reposted from: http://www.nhs.uk/news/2011/05May/Pages/statins-for-all-55-plus.aspx
crabsallover highlightskey pointscomments / links.

"All those over 55 should be offered drugs to lower cholesterol and blood pressure, according to a new study," reported BBC News. It said the report suggests that when assessing the risk of heart problems, offering treatment to all over-55s had the same results as testing for cholesterol or blood pressure problems. The authors have also argued it would be simpler and more cost-effective.