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  • I want to break free – the microenvironment and metastasis - Cancer Research UK - Science blog
    that developing the ability to spread is no easy feat for tumours they wouldn t get anywhere without a helping hand So here we ll learn about how their healthy neighbours send them on their way I get by with a little help from my friends The constant chatter between a tumour and its surroundings actively dictates its behaviour and helps it develop and flourish And eavesdropping on this gossip has taught us that the microenvironment is crucial for helping a tumour mobilise its army of mini me s throughout the body The microenvironment isn t always a bad influence at early stages of tumour development it can slow down a tumour s growth effectively giving cancer cells a molecular rap on the knuckles and telling them to play nice But as time passes these signals are drowned out by much louder persistent voices coaxing and goading tumour cells to hit the road So what changes Almost everything As we ve already seen a smouldering backdrop of inflammation causes cancer cells to gradually accumulate the genetic faults needed to cut loose from their bedfellows And as angiogenesis takes hold and provides an escape route by way of the bloodstream the microenvironment moves away from blocking metastasis and actively encourages the spread of cancer cells around the body Have stroma will travel The stroma also known as connective tissue provides structural support to tissues and organs but scientists are beginning to realise that it also plays a key role in tumour development Stromal cells are co opted to kick start angiogenesis and inflammation but they stick around to help cancer cells wriggle free from their neighbours and shimmy their way through the tumour mass They also dissolve the jelly like superglue called the extracellular matrix or the ECM holding tissues together clearing the path for tumour cells ready to escape Escapees next face the challenge of crossing blood vessel walls a process called intravasation To do this they need chemicals called proteases which chomp through the molecular masonry forming blood vessel walls Although cancer cells make plenty of proteases themselves white blood cells called macrophages also provide ample sources of the stuff finally allowing the runaway to enter the blood vessel and set sail along the bloodstream We re going to need a bigger boat The bloodstream is a risky place for metastasising cancer cells Image from a href https commons wikimedia org wiki File Playboating3 JPG target blank Wikimedia Commons a The bloodstream is a particularly dangerous environment for tumour cells it s teeming with patrolling immune cells and the brute force of blood rushing though the circulation can be lethal But help is at hand Platelets rush to the scene lured in by chemicals produced by the flailing cell They work by clumping together to form an insoluble mass a particularly useful skill when a blood clot is needed following injury But here they form a protective shield around the tumour cell guarding it against shearing or immune attack

    Original URL path: http://scienceblog.cancerresearchuk.org/2013/02/11/i-want-to-break-free-the-microenvironment-and-metastasis/ (2016-02-11)
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  • The queen in the hive - more evidence for cancer stem cells - Cancer Research UK - Science blog
    tumour and it s game over But scientists are a sceptical species Even the best ideas need to be proved before they can be accepted and the cancer stem cell hypothesis is no different Proving that stem cells play an important part in tumour growth has been fraught with difficulties finding ways to isolate them is technically challenging so sceptics have argued that the tests used are littered with inadequacy And to complicate the matter even further context is everything in biology what holds true in the breast or pancreas won t necessarily occur in say the prostate Proving the cancer stem cell theory won t be a matter of a single definitive experiment but rather the steady accrual of pieces of a complex puzzle So would the real cancer stem cell please stand up Lineage tracing experiments involve tagging individual cells with a fluorescent tag and following their fates Image courtesy Science AAAS At this very moment the puzzle is still incomplete But three important pieces were put in place this week Three research groups each took a different cancer type and asked the same question were the majority of cells in a tumour descended from a small number of ancestors as the cancer stem cell theory would predict or were they a mixed bag In other words is there a queen bee in residence Although each group worked on a different tumour type cancers of the brain bowel and skin they all made use of an ingenious biological technique called lineage tracing Individual cells are given a coloured tag that they pass on to their daughter This means that a cell s ancestry can be determined simply by looking at their colour Reporting in Nature a team of Belgian researchers led by Dr Cedric Blanpain provided compelling evidence that cancer stem cells play an important role in skin cancer His group found that in mice cells in benign skin tumours called papillomas all originated from a select few cells In the image below illustrates this the cells in red are descended from a single red tagged stem cell In this skin tumour the cells labelled red all arose from a single stem cell Credit G Driessens Meanwhile in the Netherlands Professor Hans Clevers s team focused on the cells in the bowel His team labelled single intestinal cells either red yellow blue or green When adenomas benign tumours that can progress into bowel cancer were allowed to develop they tended to be a single colour implying that they all arose from a single cell In this image the green cells are bowel stem cells courtesy H Snippert Both these studies were done in benign tumours but what about malignant tumours these are the ones that we tend to think of as cancer as they have the potential to spread In the US a team led by Professor Luis Parada also used lineage tracing to show that most of the cells in a type of brain tumour called glioblastoma

    Original URL path: http://scienceblog.cancerresearchuk.org/2012/08/03/the-queen-in-the-hive-scientists-find-more-evidence-for-cancer-stem-cells/ (2016-02-11)
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  • Expert Opinion: Professor Herbie Newell - Cancer Research UK - Science blog
    Which recent advance will have the greatest impact on cancer patients Herbie Newell I think you d probably have to identify the introduction of the human papillomavirus HPV vaccine as being the event that on a global scale is most likely to have a really significant impact Not just in the UK where to some extent we deal with cervical cancer via the screening programme but it s more important in the developing world where their healthcare systems just don t allow screening programmes and where cervical cancer remains a really serious problem By introducing a vaccine before young women become sexually active you will have a very major impact on the incidence of the disease In terms of overall mortality I think that s likely to be one of the more impressive results that we will see Cancer Research UK What do you think the future years of cancer research will bring Herbie Newell Most importantly it will bring more targeted therapies against a broader range of cancers That will improve our ability to treat the disease And there will be a better understanding of genetic predisposition improved early diagnosis and improved stratification of patients And all of these together will sustain and hopefully accelerate our ability to cure cancers Whenever I talk to the public my opening slide is always a graph showing the number of cases of cancer and the number of people dying from cancer from 1970 up to the present day That illustrates very graphically number one that the incidence of cancer is going up because of our ageing population and we are not dying from non malignant disease But most importantly number two despite this increased incidence the number of people dying from cancer has been going down steadily since the early 1990s That tells me and I think the public need to know that our strapline that Together we will beat cancer perhaps already looks a little bit out of date because together we already are beating cancer We just need more resource to continue to do this until we have this full set of tests and treatments for every stage of the cancer journey from predisposition through screening through diagnosis and through treatment When we have that full set of biomarkers and targeted therapies we ll be able to offer every cancer patient and every member of our society real optimism that cancer will be curable The other thing to emphasise is that the revolution that took place in our understanding of this disease only took place in the 1990s and exploitation of that knowledge is very much a feature of this millennium So by definition we haven t had these new treatments for long enough for the benefits to feed into long term survival figures That will come but we aren t there yet so no complacency of course but there s plenty of optimism Cancer Research UK What do you see as the greatest challenges still to be tackled in

    Original URL path: http://scienceblog.cancerresearchuk.org/2011/03/22/expert-opinion-professor-herbie-newell/ (2016-02-11)
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  • Our plan to improve genetic testing for cancer patients in the UK - Cancer Research UK - Science blog
    all the time all over the UK A partnership to beat cancer We ll do this by building a partnership between patients the research community the NHS the pharmaceutical and diagnostics industry and the government Patients who might benefit will be asked if they want to be part of the programme and if so they will get the appropriate genetic tests on their tumours and their results will be kept for research This means that as well as helping the patients we will be creating valuable research information on which genetic types of cancers are linked to better or worse response to treatments Everyone will have a role to play in this partnership The research community will help define the genes we should be looking for and link us to the latest advances around the world The NHS will identify and treat the patients based on the genetic information The pharmaceutical and diagnostic industry will help fund the testing and use the research results to develop better tests and better treatments And the government will support the programme by funding technical innovations in analysis and medicine as well as ensuring that we are creating a programme that can be used in other disease areas such as heart disease or arthritis It will be a strong team and we re really pleased by the initial positive reaction to our plans We re also building an excellent team of experts across Cancer Research UK to help us bring this partnership together Professor Peter Johnson our chief clinician is leading our scientific advisory board which includes leading scientists and clinicians in the field Dr Louise Jones the charity s expert on stratified medicine is leading the clinical and research work stream while our expert on informatics Dr Fiona Reddington is working on the data questions and Dr Fiona Hemsley from our research strategy team is looking into the technologies available for genetic testing Over the summer we ll be developing more detailed plans and learning from other examples around the world so that in September we ll be able to bring all the partners together to agree on exactly what we re going to do how many patients what cancers what genes which hospitals which testing labs and how much it will cost will all be under discussion If our initial pilots involving a few thousand patients are successful this could trigger a step change in how we research cancer testing and treatment in this country And if everything goes according to plan we would like to work with the NHS to roll this out across the country starting in 2012 This is truly what we mean when we say Together we will beat cancer James James Peach is Cancer Research UK s director of stratified medicine More information Hear our CEO Harpal Kumar on the BBC Radio 4 Today Programme after 54mins The Times Making cancer history Killing tumours may require registration Share this article More on this topic Tags Cancer in

    Original URL path: http://scienceblog.cancerresearchuk.org/2010/06/03/our-plan-to-revolutionise-cancer-care-within-five-years/ (2016-02-11)
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  • New horizons for lung cancer? - Cancer Research UK - Science blog
    annual CT scan of their chest The number of positive screening results was considerably higher in the CT scan group than the chest x ray group 18 000 vs 5 000 The vast majority of these results turned out to be false positives suspicious scans that turn out not to be cancer on further investigation in fact around 95 of positive results in both arms of the trial were false positives Although there were very few negative effects of the screening procedures themselves there were risks associated with diagnostic tests following screening Ten people from the CT scan group and 11 from the chest x ray group died within 60 days of having investigative procedures following screening A further 75 people in the CT scan group had a severe complication associated with diagnostic testing 24 in the chest x ray group The trial compared two different modes of screening rather than comparing screening with no testing So although there was no increase in overall death rate in the CT scan group compared to the chest x ray group both arms of the trial were associated with increased risks and it is not clear how the risks and benefits of these screening procedures compare with no screening There was some suggestion that lung screening results in some degree of overdiagnosis that is the diagnosis of some lung cancers that would never have progressed into more serious disease or caused any symptoms The authors are calling for more research in this area which is a sensible way forward Dr Harold Sox past President of the American College of Physicians and chair of the U S Preventive Services Task Force summed up the state of play eloquently in an opinion piece for the New England Journal of Medicine The findings signal the beginning of the end of one era of research on lung cancer screening and the start of another The focus will shift to informing the difficult patient centred and policy decisions that are yet to come The American Society of Clinical Oncology was also prompted to release a statement about these clinical trial results praising the work as an example of clinical research at its best but also echoing the sentiment of doctors from around the world But we must remember that screening is not a substitute for quitting smoking The overwhelming majority of lung cancer is caused by smoking and smoking cessation will always have a far greater impact on lung cancer deaths than any screening tool Those who wish to prevent deaths from cancer respiratory illness or heart disease the first step is to quit smoking Pain killer emerges as promising candidate for lung cancer prevention In yet more interesting but earlier stage work a different group of US scientists found evidence that a pain killer often used by people with arthritis could one day help to prevent lung cancer in former smokers We need to be cautious about these results the small clinical trial of a drug called

    Original URL path: http://scienceblog.cancerresearchuk.org/2011/07/08/new-horizons-for-lung-cancer/ (2016-02-11)
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  • Watching cancers evolve using ‘liquid biopsies’ - Cancer Research UK - Science blog
    harboured cancer cells that were resistant to paclitaxel which were now growing in response to the treatment The second breast cancer patient was treated with tamoxifen and trastuzumab aka Herceptin This resulted in increases in levels of a mutation in a gene called MED1 also previously linked to tamoxifen resistance The patient was switched to a second drug combo lapatinib and capecitabine and very quickly a second mutation in a gene called GAS6 became apparent as the cancer adapted to the treatment Again this mutation has been previously linked to resistance to drugs like lapatinib Similar pheonomena were observed in the ovarian and lung cancer patients For example after she was treated with cisplatin a mutation in a gene called RB1 became much more common in the blood of one of the ovarian cancer patients And studying the blood of the lung cancer patient who was treated with gefitinib but didn t respond showed why a new mutation had appeared in the EGFR gene the target of gefitinib causing the drug to stop working How does this help patients The search for biomarkers reliable ways to measure a tumour s response to treatment has been a long and tricky one and has tended to look for proteins secreted by tumours This new research opens the door to using DNA rather than proteins as a much more reliable biomarker for a cancer s growth This has long been talked about but never before demonstrated so elegantly It s the missing piece of the jigsaw puzzle Professor Brenton told us We can now understand what happens during treatment and how that affects the development of drug resistance On top of this its simplicity should allow the test to be used in a whole raft of clinical studies This is a test simple enough to be scaled up to 100s or 1000s of patients he said There are of course still unanswered questions and we don t know 100 per cent whether this applies to every patient but certainly for most of the main cancer types breast bowel lung ovarian etc there s good evidence that monitoring tumour DNA is feasible So what happens next We re looking to get this out of the lab and into the clinic as soon as possible and run clinical trials where we monitor patients DNA at the high quality levels in NHS hospitals so called CPA standard testing We want to work out how we can exploit changes in their tumour DNA to make solid clinical decisions that will help them he added The important leap forward he says is that DNA blood tests represent a test that won t hurt or inconvenience the patients It s a tremendously powerful technique Professor Charlie Swanton the London based Cancer Research UK researcher whose kidney cancer heterogeneity study caused a big splash last year is similarly excited It s a fabulous study he told us I have no doubt this is really game changing for cancer biomarker development

    Original URL path: http://scienceblog.cancerresearchuk.org/2013/04/08/watching-cancers-evolve-using-liquid-biopsies/ (2016-02-11)
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  • The HOPON clinical trial: a patient’s view - Cancer Research UK - Science blog
    t talk which was very annoying I had to write everything down But it only lasted a couple of days Good news Overall I was in the recovery ward just over a week As I was leaving to go home one of the nurses gave me some advice She said that the euphoria of a successful operation can be short lived and it s quite common to feel depressed after returning home And this was exactly how I felt It was very painful and I just stayed in bed So my wife rang the GP who was a great help in dealing with the anxiety and depression that had set in I started radiotherapy almost as soon as I was discharged from my surgery The radiographer said I d need six weeks of radiotherapy and then that was me done Now I ve always been a big lad and I started radiotherapy at a good weight I was told that patients lose up to half a stone on radiotherapy because it can damage your tongue and taste buds putting you off food So I tried to look after myself eating well and sticking to the aftercare from the surgery creams tablets and mouthwashes The radiotherapy flew by it just made me tired After my treatment ended I had to return every two months for a check up It was an extremely worrying time every time I saw the doctor I thought he was going to say it s come back But every two months soon became every three months then six months until finally after five years he said it was over On that final check up he said It s good news you ve got the all clear now go and enjoy your life I thanked him so much I was so happy to hear those words Joining the HOPON trial What are clinical trials Watch the animation A couple of months ago my dentist noticed a tooth was coming loose and he referred me to a specialist dentist at Liverpool hospital because of my cancer treatment That s when the dentist mentioned the HOPON trial He told me about the risk of osteoradionecrosis which can happen following dental work if you ve had radiotherapy to the jaw and how the HOPON trial was finding out if there was a way to help stop it One of the research nurses talked me through the HOPON trial He gave me all the information I needed and told me exactly what my involvement would be The nurses were all very supportive I wasn t just left alone in the wilderness I knew exactly what to expect I immediately agreed It was four weeks of hyperbaric oxygen treatment in a chamber before my tooth was taken out and then for a couple of weeks afterwards The chamber itself was comfortable and not at all frightening and the staff kept me company during the treatment I didn t even notice that the oxygen

    Original URL path: http://scienceblog.cancerresearchuk.org/2015/01/09/the-hopon-clinical-trial-a-patients-view/ (2016-02-11)
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  • The HOPON clinical trial: the research nurses’ role - Cancer Research UK - Science blog
    some form of clinical research For the HOPON trial it s slightly different because patients will first be seen in clinic by either Professor Shaw or a specialist dentist who will then refer them to us Around eight in 10 agree to join a trial which is a great success for our team Timing is everything Time can play an important part in the decision to take part in a trial or not For most of our trials patients need to make up their minds within a week of first attending our clinic Their cancer is growing so it s vital they start treatment as soon as possible In these cases we ll try to attend the patient s consultation with their doctor because it s important to see how they respond to their diagnosis and proposed treatment We try to consider every patient s mental state because signing a trial consent form on the day they get a cancer diagnosis or the day they begin treatment can be very stressful With the HOPON trial one advantage is that time is firmly on our side In these cases patients have already been successfully treated for their original cancer and are awaiting dental surgery This is rarely an emergency and sometimes a voluntary procedure such as having implants so the patients stress levels are much lower It also means they can go home and consider the trial for a couple of weeks to make sure they are happy to take part and fully understand what s involved What motivates the patients Most patients want to join HOPON because they genuinely want to help other patients in the future And because the cancer journey is over for these patients they re often more willing to take part in research they want to give something back because they ve been cured These days many patients are often much better informed and do research on the internet as soon as they get a diagnosis They certainly want information about all the treatment options open to them but whether they agree to participate in a trial is another matter What information do patients get Watch a video about taking part in a clinical trial on YouTube The doctor first approaches the patient about the clinical trial and then introduces one of us We start by talking through the clinical trial information leaflet and make sure that the patient understands not just the trial itself but what s involved in taking part The patients can choose whether they want to join and have the option to withdraw from the study at any point We are careful never to undermine patients faith in their doctors Often patients expect their consultant to know everything and tell them what s best So we explain to patients that we do a lot of research here all the time The reason we know which treatments to use when is through previous research and the only way to keep improving cancer care

    Original URL path: http://scienceblog.cancerresearchuk.org/2015/01/08/the-hopon-clinical-trial-the-research-nurses-role/ (2016-02-11)
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