tag:theconversation.com,2011:/institutions/institute-of-cancer-research-london-844/articlesInstitute of Cancer Research, London2014-04-23T11:56:49Ztag:theconversation.com,2011:article/257292014-04-23T11:56:49Z2014-04-23T11:56:49ZNHS watchdog changes could endanger new cancer drugs<figure><img src="https://images.theconversation.com/files/46851/original/5bhddb8w-1398180469.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cancer drugs like trastuzumab may not have been approved under the proposed rules.</span> <span class="attribution"><a class="source" href="http://pl.wikipedia.org/wiki/Plik:HerceptinFab.jpg">RedAndr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The National Institute for Health and Care Excellence (NICE) has published <a href="http://www.nice.org.uk/media/FE2/2B/VBA_TA_Methods_Guide_for_CONSULTATION_upload.pdf">new draft proposals</a> laying out major changes to the way it assesses whether new medicines offer value for money for the NHS. These evaluations are difficult – requiring as they do an assessment of the value of life – but are <a href="http://www.thelancet.com/commissions/delivering-affordable-cancer-care-in-high-income-countries">necessary in all healthcare systems</a> that face spiralling costs worldwide. The new proposals, however, could prevent or delay new and effective drugs from reaching patients with cancer.</p>
<p>The draft proposals show that NICE, the body that decides which drugs are available on the NHS in England and Wales, plans to change the parameters its appraisal committees use</p>
<h2>End-of-life criteria</h2>
<p>Under the current system, NICE gives extra weight in its evaluation of cost-effectiveness if drugs have shown a particular benefit in patients at the end of their lives. The calculations it uses are complex but essentially, if a drug has been shown to add three months of life expectancy to patients who have an incurable illness then the NHS may pay a price significantly higher than it would otherwise pay to roll it out.</p>
<p>The importance of end-of-life criteria is very clear: since 2009, when they were introduced, 12 cancer drugs have been approved on this basis. It is likely that many of these drugs would have been rejected in the absence of end-of-life criteria. The new system proposes to remove the criteria, instead incorporating end-of-life benefit into a broader, less defined measure of what would qualify for a higher price bracket. This risks fewer drug approvals in future.</p>
<p>In addition to removing end-of-life criteria from the drug appraisal system, NICE has also suggested it will remove specific consideration of how innovative a new treatment is. I worry that both of these changes will result in cancer drugs being rejected when under the current system they would have been approved. This could deny cancer patients access to life-extending drugs and dramatically reduce the likelihood of achieving the cancer cures of the future.</p>
<p>At The Institute of Cancer Research in London, we have direct experience of the value of the current drug approval process. For example, a groundbreaking new prostate cancer drug called abiraterone that we discovered has helped thousands of sufferers. Initially approved for patients with late-stage prostate cancer resistant to existing drugs, abiraterone has since gone on to <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1209096">benefit patients in earlier stages of the disease</a>. Yet abiraterone would probably not be approved under the proposed changes.</p>
<h2>Stifling innovation risk</h2>
<p>By omitting specific consideration of innovation, the new guidelines will discourage the more creative, high-risk drug discovery research. Previously, NICE’s cost-benefit analysis allowed innovation to be rewarded by paying more for innovative drugs, although the definition of innovation was quite loose. In the new proposals, the chance to formalise the importance of developing novel treatment types has been overlooked. The consequences could be very damaging.</p>
<p>Innovative cancer drugs are those with new mechanisms of action – particularly precision medicines that act on new molecular targets derived from basic cancer biology research and the latest genomics studies, and also those that exploit cutting edge immunological research. Innovative drugs are tremendously important because they offer the possibility of major breakthroughs that cannot be achieved with those that simply mimic or marginally <a href="http://www.ncbi.nlm.nih.gov/pubmed/22235862">enhance the effects of existing drugs</a>.</p>
<p>In recent years, our understanding of cancer has increased dramatically and we’ve learnt that cancer medicine <a href="http://www.ncbi.nlm.nih.gov/pubmed/23361103">works best when it is personalised</a> to individuals. One of the best examples of developing this kind of personalised, precision medicine is trastuzumab. This has helped extend the lives of breast cancer patients with high tumour levels of the HER2 marker, a protein which drives the growth of their cancer. HER2 is also important in a proportion of stomach cancers and NICE approved trastuzumab use in these patients on the NHS under the old end-of-life criteria. Again, this might not have happened under the new draft proposals. </p>
<h2>Tackling drug resistance</h2>
<p>Innovation is also essential if we are to overcome the massive problem of drug resistance – the most important challenge facing cancer drug discovery and development today. We now know that resistance arises because cancers are extraordinarily variable and versatile in evolving mechanisms to get around the effects of both molecular targeted and conventional drugs.</p>
<p>An example of an innovative approach to tackle resistance is the discovery and development of <a href="http://www.ncbi.nlm.nih.gov/pubmed/22215907">Hsp90 inhibitors</a> – a totally new type of drug that we, and only a few other research centres worldwide, have pioneered. These inhibitors have the exciting ability to target several different cancer molecular weaknesses at once, and so can overcome or even prevent drug resistance.</p>
<p>It took costly, high-risk research to develop Hsp90 inhibitors and they have progressed from being a poorly appreciated drug target to one of the most actively pursued in the drug industry today. Leading Hsp90 inhibitors have shown very encouraging results in trials of patients with HER2-positive breast cancers that have become resistant to trastuzumab and patients with non-small cell lung cancer who have become resistant to the widely used molecular targeted drugs erlotinib and crizotinib.</p>
<p>It would be very disappointing if this sort of innovation is not rewarded when it comes to deciding if the NHS will pay so that patients can benefit.</p>
<p>Another crucial benefit arising from both the end-of-life criteria and the current guidance that promotes innovation is that drugs originally approved for “end-of-life” use very often turn out, later on, to benefit patients with earlier stage cancer – as noted above with abiraterone. Also, the current system provides an initial route into the NHS for innovative drugs, which can then subsequently be shown to be effective in the harder-to-treat cancers, especially by combining them with other drugs. New drug combinations could hold the key to tackling drug resistance for many cancers and encouraging innovation is critical for this.</p>
<h2>Crucial time</h2>
<p>The proposed NICE changes could mean a backward step at a crucial point in the history of cancer drug discovery and development, research and development costs of which are of course very high. Clinical trials are the most expensive part and failure in these is still depressingly common. But the high costs and failure rates are mostly a result of the old one-size-fits-all approach where potential drugs are not targeted to the specific molecular characteristics of individual patients. </p>
<p>The costs of developing personalised drugs will eventually fall because clinical trials supporting drug approval will be smarter, smaller and shorter. Instead of relying on a small number of one-size-fits-all blockbusters, companies will have a larger portfolio of lower volume, personalised precision drugs that are targeted to smaller patient populations. The transition to personalised drugs with reduced prices will take time, but this must happen.</p>
<p>Nonetheless, it’s a hugely exciting time, both in basic cancer research and in creative drug discovery and development. We must not let overly restrictive regulation deprive patients of access to innovative and life-prolonging drugs that are being developed now and in the future.</p><img src="https://counter.theconversation.com/content/25729/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Paul Workman works at The Institute of Cancer Research (ICR), London which is involved in cancer drug discovery and development research and operates a Rewards to Discoverers scheme. ICR receives income from sales of abiraterone (Janssen) that are reinvested in research. ICR has licensed intellectual property on HSP90 inhibitors to Vernalis and Novartis and may benefit from future income for research. Paul Workman has previously been a consultant for Novartis and Chroma Therapeutics and is a consultant for Astex Pharmaceuticals and Nextech Ventures. He holds shares in Chroma Therapeutics. He has received grant funding from Cancer Research UK, The Wellcome Trust, Medical Research Council, Vernalis, Janssen, Astex Pharmaceuticals, Chroma Therapeutics and the Kidani Trust.</span></em></p>The National Institute for Health and Care Excellence (NICE) has published new draft proposals laying out major changes to the way it assesses whether new medicines offer value for money for the NHS. These…Paul Workman, Head of the Division of Cancer Therapeutics, Institute of Cancer Research, LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/218752014-01-09T14:25:36Z2014-01-09T14:25:36ZNanoparticles cause cancer cells to die and stop spreading<figure><img src="https://images.theconversation.com/files/38743/original/922gs5tj-1389267928.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Good news, we have stopped the spread of cancer.</span> <span class="attribution"><span class="source">National Cancer Institute</span></span></figcaption></figure><p>More than nine in ten cancer-related deaths occur because of metastasis, the spread of cancer cells from a primary tumour to other parts of the body. While primary tumours can often be treated with radiation or surgery, the spread of cancer throughout the body limits treatment options. This, however, can change if work done by Michael King and his colleagues at Cornell University, delivers on its promises, because he has developed a way of hunting and killing metastatic cancer cells.</p>
<p>When diagnosed with cancer, the best news can be that the tumour is small and restricted to one area. Many treatments, including non-selective ones such as radiation therapy, can be used to get rid of such tumours. But if a tumour remains untreated for too long, it starts to spread. It may do so by invading nearby, healthy tissue or by entering the bloodstream. At that point, a doctor’s job becomes much more difficult.</p>
<p>Cancer is the unrestricted growth of normal cells, which occurs because mutations in normal cell cause it to bypass a key mechanism called apoptosis (or programmed cell death) that the body uses to clear old cells. However, since the 1990s, researchers have been <a href="http://www.economist.com/blogs/babbage/2013/02/cancer-drugs">studying</a> a protein called TRAIL, which on binding to the cell can reactivate apoptosis. But so far, using <a href="http://www.ncbi.nlm.nih.gov/pubmed/19149761">TRAIL as a treatment</a> of metastatic cancer hasn’t worked, because cancer cells suppress TRAIL receptors.</p>
<p>When attempting to develop a treatment for metastases, King faced two problems: targeting moving cancer cells and ensuring cell death could be activated once they were located. To handle both issues, he built fat-based nanoparticles that were one thousand times smaller than a human hair and attached two proteins to them. One is E-selectin, which selectively binds to white blood cells, and the other is TRAIL.</p>
<p>He chose to stick the nanoparticles to white blood cells because it would keep the body from excreting them easily. This means the nanoparticles, made from fat molecules, remain in the blood longer, and thus have a greater chance of bumping into freely moving cancer cells. </p>
<p>There is an added advantage. Red blood cells tend to travel in the centre of a blood vessel and white blood cells stick to the edges. This is because red blood cells are lower density and can be easily deformed to slide around obstacles. Cancer cells Have a similar density to white blood cells and remain close to the walls, too. As a result, these nanoparticles are more likely to bump into cancer cells and bind their TRAIL receptors.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/38741/original/mstnbd4s-1389266904.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/38741/original/mstnbd4s-1389266904.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=346&fit=crop&dpr=1 600w, https://images.theconversation.com/files/38741/original/mstnbd4s-1389266904.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=346&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/38741/original/mstnbd4s-1389266904.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=346&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/38741/original/mstnbd4s-1389266904.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=434&fit=crop&dpr=1 754w, https://images.theconversation.com/files/38741/original/mstnbd4s-1389266904.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=434&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/38741/original/mstnbd4s-1389266904.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=434&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Leukocytes are WBCs and liposomes are nanoparticles.</span>
<span class="attribution"><span class="source">King/PNAS</span></span>
</figcaption>
</figure>
<p>King, with help from Chris Schaffer, also at Cornell University, tested these nanoparticles in mice. They first injected healthy mice with cancer cells, and then after a 30-minute delay injected the nanoparticles. These treated mice developed far fewer cancers, compared to a control group that did not receive the nanoparticles. </p>
<p>“Previous attempts have not succeeded, probably because they couldn’t get the response that was needed to reactivate apoptosis. With multiple TRAIL molecules attached on the nanoparticle, we are able to achieve this,” Schaffer said. The work has been published in the <a href="http://dx.doi.org/10.1073/pnas.1316312111">Proceedings of the National Academy of Sciences</a>.</p>
<p>While these are exciting results, the research is at an early stage. Schaffer said that the next step would be to test mice that already have a primary tumour. </p>
<p>“While this is an exciting and novel strategy,” according to Sue Eccles, professor of experimental cancer therapeutics at London’s Institute of Cancer Research, “it would be important to show that cancer cells already resident in distant organs (the usual clinical reality) could be accessed and destroyed by this approach. Preventing cancer cells from getting out of the blood in the first place may only have limited clinical utility.”</p>
<p>But there is hope for cancers that spend a lot of time in blood circulation, such as blood, bone marrow and lymph nodes cancers. As Schaffer said, any attempt to control spreading of cancer is bound to help. It remains one of the most exciting areas of research and future cancer treatment.</p><img src="https://counter.theconversation.com/content/21875/count.gif" alt="The Conversation" width="1" height="1" />
More than nine in ten cancer-related deaths occur because of metastasis, the spread of cancer cells from a primary tumour to other parts of the body. While primary tumours can often be treated with radiation…Akshat Rathi, Former Science and Data Editor, The ConversationLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/200502013-11-11T14:51:46Z2013-11-11T14:51:46ZArtificial intelligence uses biggest disease database to fight cancer<figure><img src="https://images.theconversation.com/files/34807/original/jvqm9qpq-1383933807.jpg?ixlib=rb-1.1.0&rect=0%2C2%2C1600%2C960&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Finding links between vast amounts of cancer data could drive new drugs.</span> <span class="attribution"><span class="source">Fran Simó</span></span></figcaption></figure><p>We live in an exciting era where new technologies are allowing us to amass huge quantities of data about cancer. And vast databases containing the genetic profiles of tumours and other information have the potential to uncover potential new drugs.</p>
<p>The International Cancer Genome Consortium <a href="http://icgc.org/">is profiling</a> up to 20,000 cancer patients already and the world’s largest single database of cancer patients has <a href="https://www.gov.uk/government/news/worlds-largest-cancer-database-launched-by-phe">just been launched</a>. It will combine near real-time cancer data on the 350,000 cancers diagnosed each year in England, along with detailed clinical information and over 11m historical cancer records.</p>
<p>With all this information, you might expect new breakthroughs in cancer treatment to come in thick and fast. But the more of these goldmines of raw material we have, the harder it actually becomes to make sense of it. To do this, we need a whole battery of other information – like how different drugs may interact with patients’ genes, which genes are likely to be suitable for drug development, and what key lab experiments will get us on our way to a new drug. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/34810/original/wf6m5dm3-1383974443.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/34810/original/wf6m5dm3-1383974443.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=507&fit=crop&dpr=1 600w, https://images.theconversation.com/files/34810/original/wf6m5dm3-1383974443.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=507&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/34810/original/wf6m5dm3-1383974443.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=507&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/34810/original/wf6m5dm3-1383974443.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=637&fit=crop&dpr=1 754w, https://images.theconversation.com/files/34810/original/wf6m5dm3-1383974443.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=637&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/34810/original/wf6m5dm3-1383974443.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=637&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Making connections.</span>
<span class="attribution"><span class="source">canSar</span></span>
</figcaption>
</figure>
<p>To make this easier we’ve developed a unique <a href="http://cansar.icr.ac.uk">canSAR database</a> to link the raw goldmines of genetic data to a whole raft of independent chemistry, biology, patient and disease information. It collates billions of experimental results from around the world including ones on the presence of genetic mutations, the levels of genes and their resultant proteins in a tumour, and the measured activity of a compound or drug on tested proteins. </p>
<p>The system then “translates” these data into a common language so that they can be compared and linked. It can even explore the patterns of interaction between proteins in a cell using similar systems that are used to explore human interactions in social networks. </p>
<p>Once these masses of data are collated and translated, canSAR then uses sophisticated machine learning and artificial intelligence to draw paths between them, predict risks and make drug-relevant suggestions that can be tested in the lab.</p>
<p>It’s a bit like predicting the likely winners of a 100m Olympic race. The computer first “learns” the important factors from past race winners such as cardiovascular fitness, muscle mass, past performance, their training schedule, and then it uses this learning to rank new athletes based on how well they fit the profile of winners. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/34811/original/tksjrrrm-1384010441.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/34811/original/tksjrrrm-1384010441.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/34811/original/tksjrrrm-1384010441.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/34811/original/tksjrrrm-1384010441.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/34811/original/tksjrrrm-1384010441.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/34811/original/tksjrrrm-1384010441.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/34811/original/tksjrrrm-1384010441.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">And they’re off.</span>
<span class="attribution"><span class="source">Eviltomthai</span></span>
</figcaption>
</figure>
<p>Using canSAR potential cancer targets can be spotted by bringing lots of sources of existing data together in one place and deciphering important properties from previous successful drug targets. We need state-of-the-art high-performance computing to be able to crunch the billions of numbers to make these predictions. We then make the results available so they can be used by researchers.</p>
<p>Of course, a resource is only a success if it is widely used. So the database has been made available free to all and we expect it to become a staple in the cancer researcher’s toolkit. A much smaller prototype database, was used by 26,000 unique users in more than 70 countries around the world. The prototype <a href="http://www.ncbi.nlm.nih.gov/m/pubmed/23274470/">was used to identify</a> 46 potentially “druggable” cancer proteins that had previously been overlooked. Some of these have since gained interest in the community and are being better studied. canSAR will be able to do this kind of work on a much larger scale.</p>
<p>And one of the most valuable immediate benefits is that it helps to ask “what if” questions and generates hypotheses than can be tested in the lab. There are many decisions that need to be made on the path to discovering and developing a drug. Linking all this information will help speed up these decisions and make the calls that are most likely to get us faster towards patient benefit. </p><img src="https://counter.theconversation.com/content/20050/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bissan Al-Lazikani receives funding from Cancer Research UK.</span></em></p>We live in an exciting era where new technologies are allowing us to amass huge quantities of data about cancer. And vast databases containing the genetic profiles of tumours and other information have…Bissan Al-Lazikani, Team Leader in Computational Biology and Chemogenomics, Institute of Cancer Research, LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/152122013-06-14T14:36:14Z2013-06-14T14:36:14ZSupreme Court BRCA patenting decision: experts respond<figure><img src="https://images.theconversation.com/files/25592/original/gkwwz66y-1371219058.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Angelina Jolie has a double mastectomy after discovering she carried a mutation of the BRAC1 gene.</span> <span class="attribution"><span class="source">Dominic Lipinski/PA Wire</span></span></figcaption></figure><p>Millions of women in the US will have access to affordable genetic screening for cancer after the US Supreme Court ruled that a commercial company cannot patent human genes.</p>
<p>The screening tests for mutations in the BRCA1 and BRCA2 genes that increase someone’s risk of developing breast cancer. Actress Angelina Jolie recently revealed that she had undergone a double mastectomy after the test revealed she had an 87% chance of getting breast cancer. </p>
<p>But since the 1990s, the BRCA1 and BRCA2 genes have been patented by Myriad, a Utah-based company, which charged at least US$3000 (£1,900) a time for the test. It argued that removing the patents would stifle innovation.</p>
<p>But after a successful legal challenge to the company’s monopoly - unanimously upheld by judges - US labs will now be able to carry out the tests for less than US$200 (£127) a time.</p>
<p>The <a href="http://www.supremecourt.gov/opinions/12pdf/12-398_8njq.pdf">court upheld patents</a> for synthetic cDNA “because it is not naturally occurring”.</p>
<p>What does the ruling mean for women who may be at risk of cancer? And will it stifle research leading to less? A panel of experts responds below</p>
<hr>
<p><strong>Professor Anneke Lucassen, Clinical Geneticist, University of Southampton:</strong></p>
<p>Looking at the reaction to the news and on Twitter the decision is seen as a victory. The reason health professionals and patients are happy is because you can’t do genetic tests on those genes without paying a fee to Myriad.</p>
<p>But companies can still patent synthetic DNA, and I wonder what this will mean in practice. In order to do DNA tests you have to copy it first. Because you can’t sequence it directly, you have to copy the naturally occurring [DNA] compound to analyse it. Those copies aren’t covered by the ruling as far as I can see. If that’s the case then they can still patent those and this isn’t as big a victory as the headlines are making out. There’s still a loophole. </p>
<p>In the UK and Europe the decision wasn’t so eagerly awaited as we weren’t strangled by Myriad. In the US they had to pay around $3000, whereas here it costs some £500 a go because the European Patent Office doesn’t observe US rules. In practice we haven’t had to pay Myriad for testing. But the principle of not being able to patent people’s genetic code is of course as welcome here as in the US.</p>
<hr>
<p><strong>Professor Marcus Pembrey, Emeritus Professor of Paediatric Genetics, University of Bristol</strong></p>
<p>It’s good news. I’m a clinical geneticist in paediatrics and I’ve dealt with families with inherited disorders. We were involved in early work on haemophilia and other types of monogenic conditions, which are genetically determined and only involved only one altered gene, to help families who had this problem running through them. It was a great surprise at the time that companies were able to patent. </p>
<p>I’m not against patents. But it might be in the clever way someone comes up with for analysing it - as happened with polymerase chain reaction which was a clever idea of taking a bit of DNA and amplifying it so you could look at lots of DNA at the same time. That was a good example of a patent and a clever idea that pushed the research field forward very quickly.</p>
<p>Trying to patent gene sequences and the fault in them - it’s a naturally occurring thing and not patentable. You might argue that it’s a legal issue not an ethical one but there’s an element of ethics. It’s trying to extract additional profit from what to some extent is a human right.</p>
<hr>
<p><strong>Professor Alan Ashworth, head of the Institute of Cancer Research and part of the team who discovered BRCA2:</strong></p>
<p>The argument that innovation will be stifled if there are no rewards for “invention” is particularly pernicious. Commercial organisations can be exceptionally innovative and it is only right that this is rewarded. But patenting is not the only way to ensure innovation. </p>
<p>Tests for potentially fatal BRCA mutations are already saving lives by diagnosing women at highest risk of developing breast and ovarian cancer. By identifying women who carry high-risk BRCA mutations, doctors can help them make decisions on their future treatment, for example by offering a preventative mastectomy.</p>
<p>When we found the BRCA2 gene our aim was that our discovery was used to help cancer patients.</p>
<hr>
<p><strong>Professor Julian Savulescu, Uehiro Chair in Practical Ethics and Director, Institute for Science and Ethics, Oxford University:</strong></p>
<p>I don’t think it is clear at the moment whether this decision is good or bad. Patents are there for a period of time and the misunderstanding people have is that these genes are owned by the company. The patents are held for seven years to enable companies to recoup investment. So during that seven years you could say research is restricted.</p>
<p>Create mechanisms to make it worthwhile. It may be that patenting isn’t the best way but it’s an empirical issue. The legal system might be irrational but it is very important to know what the consequences are. It’s very easy to say it should be free.</p>
<p>Patents are all of limited timespan. It could be that in the longer term this is the best way to maximise investment. I do think you need to provide a mechanism. We don’t live in a Communist state and I’m concerned you have very long term consequences on research.</p>
<p>On the other hand we want as many people as possible to access these tests and make decisions on the basis of them. Angelina Jolie did a good thing in raising public awareness of these possibilities. But it’s hard to know at this point whether this ruling will have an impact.</p><img src="https://counter.theconversation.com/content/15212/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alan Ashworth is Chief Executive of the Institute of Cancer Research and receives a number of relevant grants through the organisation</span></em></p><p class="fine-print"><em><span>Julian Savulescu has received funding from the Wellcome Trust for a Hinxton Collaboration group meeting on patents and intellectual property</span></em></p><p class="fine-print"><em><span>Marcus Pembrey receives funding from the Medical Research Council</span></em></p><p class="fine-print"><em><span>Anneke Lucassen does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Millions of women in the US will have access to affordable genetic screening for cancer after the US Supreme Court ruled that a commercial company cannot patent human genes. The screening tests for mutations…Alan Ashworth, Chief Executive, Institute of Cancer Research, LondonAnneke Lucassen, Professor of Clinical Genetics, University of SouthamptonJulian Savulescu, Sir Louis Matheson Distinguished Visiting Professor, Monash UniversityMarcus Pembrey, Emeritus Professor of Paediatric Genetics, University of BristolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/150632013-06-10T13:59:24Z2013-06-10T13:59:24ZGenes help spread of shape-shifting skin cancer cells<figure><img src="https://images.theconversation.com/files/25288/original/k55tx5kf-1370871553.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C889%2C493&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The humble fruit fly: teaching us more about melanoma skin cancer.</span> <span class="attribution"><span class="source">Flickr/John Tann</span></span></figcaption></figure><p>Melanomas may be less common than other skin cancers but their ability to become malignant and spread to other parts of the body makes them some of the deadliest if not caught early. </p>
<p>More than <a href="http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Melanoma/Melanoma.aspx">10,000 people in the UK</a> are diagnosed each year and a fifth of these - more than 2,000 people - die from a malignant melanoma that has spread. </p>
<p>Now researchers have <a href="http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb2764.html">identified a set of genes</a> that regulate the ability of melanoma cells to rapidly shift between two shapes, enabling them to escape from the skin and spread to other areas such as the liver, lungs and brain.</p>
<p>Melanomas usually start in the skin because of tumours that begin in the melocytes - responsible for producing melanin and the colour of our skin, which can lead to distinctive dark colour. It can start in normal-looking skin but also in moles.</p>
<p>Melanoma cells adopt different shapes to squeeze between healthy cells. A rounded shape allows them to travel through the bloodstream, but the cells then take on an elongated shape to travel through harder tissues such as bone. Until now it was not known how they changed shape or switched between the two.</p>
<p>Researchers at the Institute of Cancer Research and Weill Cornell Medical College in Houston, Texas, used fruit flies to investigate how the cells work. Fruit fly cells take on five different shapes as they grow. By switching off specific genes, the researchers were able to change the mix of shapes in the cells to identify several that controlled cell shape.</p>
<p>In melanoma cells, switching off these cells had a similar effect. Switching off one called PTEN increased the number of cells that were elongated rather than rounded.</p>
<p>“We think that metastatic melanoma cells lose their PTEN function so that they can increase their shape-shifting ability, which in turn enables them to move to many different tissues within the body,” Dr Chris Bakal, a Wellcome Trust research fellow at the ICR, said. “PTEN loss is common in all cancers.”</p>
<p>Mutations in the PTEN gene, and in some cases its absence, plays a part in the development of a number of cancers. It is switched off in one in eight people with melanoma.</p>
<p>“We’re implicating PTEN loss as altering shape and proliferation,” Bakal said. “Cancers normally change shape but the loss of PTEN gives them the advantage of shape shifting faster.”</p>
<p>“We identified PTEN but also dozens of other genes that also play a part.” </p>
<p>In the UK, melanoma is the most common cancer in people aged 15–34 - particularly in women - and is on the rise. <a href="http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Melanoma/AboutMelanoma/Riskfactorsandcauses.aspx">UV radiation</a> from too much sun exposure and not enough sunscreen on holiday is one of the main causes, as is the use of sunbeds. People who regularly have sunburn, especially where the skin blisters, are more at risk. </p>
<p>“Melanomas are dangerous because unlike most types of cancer cells they don’t follow two steps to become invasive,” Professor Dorothy Bennett, a cell biologist from St George’s, University of London, said. “As soon as they become invasive, they’re capable of <a href="http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic">metastasising</a> [spreading to other parts of the body]. In other kinds of cancers, the cancer cells first get outside the tumour into nearby tissues, which is called becoming malignant, or invading. But they need another step before they metastasise.”</p>
<p>“We don’t know for sure but we believe it spreads so easily because pigment cells are migratory cells. In a human embryo, and in all mammals, pigment cells develop somewhere in the middle back before moving. They have a natural migratory trend so as soon as they’re able to divide excessively, forming a melanoma, they become dangerous.</p>
<p>"Another nasty feature of melanoma cells seems to be their ability to colonise almost any other area; bones and the brain for example,” she said. </p>
<p>“Other cancer cells usually spread to specific sites more than others. Melanomas are easy to treat if you get them early. Many are easy to cut off. Surgery is the best treatment if caught early but if it grows to 2-3mm thick it might be too late. How fast it grows depends on what kind of melanoma it is.</p>
<p>Surgery is the most common cure for melanoma, Mark Middleton, Professor of Experimental Medicine at Cambridge University said. Five out of six melanomas are cured by surgery. But treatment for more advanced melanomas have improved over the last three years.</p>
<p>"The role of PTEN varies from cancer to cancer. The absence of it in a cancer such as melanoma is very important, but not so much in bowel cancers. It has importance for brain and breast cancer. Whether it is missing or no forms one of the bases of how we classify cancer. Not having it is not necessarily a bad thing. It’s still far from clear.”</p><img src="https://counter.theconversation.com/content/15063/count.gif" alt="The Conversation" width="1" height="1" />
Melanomas may be less common than other skin cancers but their ability to become malignant and spread to other parts of the body makes them some of the deadliest if not caught early. More than 10,000 people…Jo Adetunji, EditorLicensed as Creative Commons – attribution, no derivatives.