The cutting-edge cancer research which could save thousands of lives
by Madeleine Brindley, Western Mail
Jan 2 2012
================================================
Scientists at the Cancer Research UK Centre in Cardiff are carrying out cutting-edge research into the disease. Health Editor Madeleine Brindley profiles some of their work
THE Cancer Research UK Centre in Cardiff concentrates its groundbreaking work on urological, breast and blood cancers and on cancer prevention.
Dr Chris Pepper, is a reader in haematology at Cardiff University and leads the centre’s research into chronic lymphocytic leukaemia (CLL).
He said: “Our research breaks down into three main areas, all of which are very patient-focused. The vast majority of our research is done by looking at cells from patients who come into the clinic.
“The first of those areas is the identification of new prognostic markers.
“It is really important to identify up front, when a patient first presents with disease, whether they are going to require early treatment or whether we can just monitor their disease.
“We’re entering an era of personalised medicine, and the ability to accurately determine the clinical course of an individual patient’s disease is a major priority.
“This is particularly pertinent in CLL because of the very different clinical outcomes associated with this disease.
“The worst type of CLL is just as bad as any leukaemia – survival rates are less than two years.
“In contrast, about a third of the patients we see have a leukaemia that never progresses and they will probably die of old age rather than from the disease,” he added.
“We’re now trying to look at the biology of the disease to see if we can identify those patients who need treatment right now – probably about a third – and another third who will progress at some point down the line.
“We’ve made some significant progress down that road in work I’ve been doing with my colleagues Dr Duncan Baird and Dr Chris Fegan.
“We now understand that some patients undergo an awful lot more cell proliferation, meaning the cells divide more and more, although this doesn’t necessarily manifest itself in an increased tumour burden, so can’t be detected by a routine blood test.
“We’ve been looking at telomeres, which are found on the ends of chromosomes and are like a biological clock, because they shorten every time a cell divides.
“Their primary role is to protect the integrity of our genetic material, but as they get shorter they start to lose their protective function.
“We’ve discovered that when they reach a certain length they become unstable, and the chromosomes stick together when the cells divide, driving genetic instability.
“The chromosome material gets muddled up as a result, genes get deleted or moved.
“We think this is the key driver of disease progression in many cancers, not just CLL.
“As these cells keep dividing, they become more and more unstable, which confers a bad prognosis to a patient, because their genetic material is constantly being altered, making the cancer much more difficult to treat.
“In addition to telomere length, we have also identified a molecule called NF-kappaB,” he revealed.
“This molecule is a master regulator of hundreds of different genes, many of which are associated with the control of processes that could result in cancerous changes.
“We’ve shown that by measuring the levels in patients, it allows us to predict whether an individual patient will respond to conventional chemotherapy.
“If they have high levels, they relapse very quickly on conventional therapy.
“The second part of our work is basic tumour cell biology.
“We’re trying to understand what’s driving the malignancy; why do some patients have a very stable disease while others rapidly progress and require chemotherapy.
“It has become increasingly clear that one of the key determinants of disease progression is the ability of the tumour cell to change the micro-environment they exist in. We want to know how.
“People tend to think of cancer as a foreign invader, but it’s not.
“A cancer is essentially yourself, but it has changed subtly from the other cells in your body, which makes it very difficult to identify and to eradicate using your body’s own defence mechanisms.
“In the case of CLL, the disease actually uses the immune system to promote cancer cell survival.
“Work that we have recently published with another colleague, Dr Steve Man, indicates that in the early stages of the disease the immune system probably tries to mount a response to the cancer but once that fails the tumour grows.
“Those same immune system cells are changed by the environment the cancer cells create, making them produce different chemicals which support the growth and the survival of the tumour, making it difficult to treat.
“Our third area of work is to develop novel therapies – we have been involved in the development of a number of new treatments for CLL, including more targeted agents that specifically attack the tumour cell.
“The latest class of drugs we are testing are able to alter the environment tumour cells live and grow in to make them more sensitive to the standard therapies.
“These drugs look set to make a valuable addition to the treatment options for this disease in the near future and we hope that some of them will be trialled here in Cardiff.”
RESEARCH into prostate cancer at the centre focuses on two distinct areas – exosomes and the ongoing STAMPEDE trial.
Although separate areas, both relate to the drive to develop more targeted treatments which respond to individual patients’ disease.
Professor Malcolm Mason, who is leading the research, said: "We want to know why some prostate cancer tumours spread to other parts of the body, when others don’t and we’re also interested in ways we can speed up the development of new drugs.
"When doing drug trials, we rely on conventional measures – we basically give a drug to a patient and if their tumour gets smaller, the drug gets developed further.
"Prostate cancer often spreads to the bones and it can be difficult to assess whether bone metastases are getting smaller.
"Another issue is that trials can take a long time because prostate cancer can be slow growing sometimes – a prostate cancer trial has just been published in The Lancet, which I started putting patients into in the mid 1990s. Somehow we need to make that time shorter.
"There are new biological markers we can use to see whether a patient is responding to treatment – we’re doing this in Cardiff with the financial help of a lot of funders, including Cancer Research Wales, which is putting money into prostate cancer research.
"We are looking at exosomes, which are very tiny – a fraction of the size of a cell – membranes produced by all cells, which have all sorts of things inside them.
"From our point of view, is this a way to measure bio-markers and get a faster indication of whether a patient is responding to treatment?
"We have been able to measure exosomes in the urine of patients and we can see them disappear as they have treatment.
"But there are still technical difficulties in terms of assessing them and we’re still a long way from seeing it in use in a clinic."
STAMPEDE is an international trial designed to assess the safety and effectiveness of hormone therapy in the treatment of prostate cancer. Cardiff is one of the main research centres in the trial – the largest of its kind in the world, involving more than 2,000 patients currently.
Prof Mason added: "My primary role is clinical research and clinical trials – Cardiff is the second highest place in the UK in terms of recruiting patients to STAMPEDE, which is run by the Medical Research Council and funded by Cancer Research UK.
"It compares hormone treatments and hormone therapy plus other drugs, such as chemotherapy, bisphosponates, which prevent bone mass loss and new drugs like abiraterone.
"There will be a lot of information from this trial and some of the first data has already been presented. It’s a very important part of what we’re doing.
RESEARCH into a gene called MBD2 could lead to new treatments for colon cancer, after experts discovered that switching it off prevents tumours from forming.
The breakthrough has been described as a "potential Achilles’ heel" by lead researcher Professor Alan Clarke.
It comes from the work at the Cancer Research UK Centre in Cardiff into how genes and proteins are involved in the formation of cancer.
Prof Clarke said: "The interesting thing about cancer is that one of its primary features is to turn off a number of defensive mechanisms. As the cancer develops, these defensive mechanisms are got around, usually because the genes are switched off or deactivated."
The first breakthrough came with the discovery of the DNMT1 gene, which, when switched off meant that cancers couldn’t develop.
But deactivating DNMT1 also had a significant effect on other bodily functions, meaning it would not make a good target for cancer therapies.
MBD2 belongs to a family of proteins which turn off other genes and research carried out in Cardiff has found that deactivating it prevents colon tumours from developing.
"It’s fantastic and does it with virtually 100% efficiency," Prof Clarke said. "And, taking out MBD2 isn’t that damaging to other tissues and systems – it appears to be tolerated reasonably well.
"Therefore, if we were to have a therapy targeting MBD2, any off-target effects would be limited."
The research team has been examining the impact of MBD2 by creating mice which lack the gene. But many questions remain unanswered.
Prof Clarke said: "We have to show that if you don’t have MBD2 then the likelihood of getting a tumour is much reduced. And we don’t know if you take out MBD2 from a tumour whether it will disappear.
"We’ve been trying to develop a drug that specifically targets MBD2 but, unfortunately, attempts have not been successful because it’s a very difficult protein.
"We think that MBD2 deficiency suppresses tumorigenesis by failing to turn off a number of genes – some these will be important. We’re trying to delve down and find out which of the genes it regulates are important.
"We have a potential Achilles’ heel here to stop tumours forming and we’re also trying to find a drug target.
"We can imagine that this will be useful for patients who have had a tumour and have had therapy but who have a chance of relapsing. But we’re also testing the notion that regulating MBD2 will cause tumours to regress."
Prof Clarke added: "The remarkable thing about the way we treat cancer is that we’re stuck with pretty much ancient technology.
"We mostly use poisons but although we have made progress with virtually all forms of cancer in terms of improving treatment, if we are going to make a huge step change it will have to come from a better understanding of the mechanisms that lead to cancer.
"That will come from a molecular understanding of cancer – if we really understand the molecular basis we can create drugs that make a big difference rather than small, incremental differences."
by Madeleine Brindley, Western Mail
Jan 2 2012
================================================
Scientists at the Cancer Research UK Centre in Cardiff are carrying out cutting-edge research into the disease. Health Editor Madeleine Brindley profiles some of their work
THE Cancer Research UK Centre in Cardiff concentrates its groundbreaking work on urological, breast and blood cancers and on cancer prevention.
Dr Chris Pepper, is a reader in haematology at Cardiff University and leads the centre’s research into chronic lymphocytic leukaemia (CLL).
He said: “Our research breaks down into three main areas, all of which are very patient-focused. The vast majority of our research is done by looking at cells from patients who come into the clinic.
“The first of those areas is the identification of new prognostic markers.
“It is really important to identify up front, when a patient first presents with disease, whether they are going to require early treatment or whether we can just monitor their disease.
“We’re entering an era of personalised medicine, and the ability to accurately determine the clinical course of an individual patient’s disease is a major priority.
“This is particularly pertinent in CLL because of the very different clinical outcomes associated with this disease.
“The worst type of CLL is just as bad as any leukaemia – survival rates are less than two years.
“In contrast, about a third of the patients we see have a leukaemia that never progresses and they will probably die of old age rather than from the disease,” he added.
“We’re now trying to look at the biology of the disease to see if we can identify those patients who need treatment right now – probably about a third – and another third who will progress at some point down the line.
“We’ve made some significant progress down that road in work I’ve been doing with my colleagues Dr Duncan Baird and Dr Chris Fegan.
“We now understand that some patients undergo an awful lot more cell proliferation, meaning the cells divide more and more, although this doesn’t necessarily manifest itself in an increased tumour burden, so can’t be detected by a routine blood test.
“We’ve been looking at telomeres, which are found on the ends of chromosomes and are like a biological clock, because they shorten every time a cell divides.
“Their primary role is to protect the integrity of our genetic material, but as they get shorter they start to lose their protective function.
“We’ve discovered that when they reach a certain length they become unstable, and the chromosomes stick together when the cells divide, driving genetic instability.
“The chromosome material gets muddled up as a result, genes get deleted or moved.
“We think this is the key driver of disease progression in many cancers, not just CLL.
“As these cells keep dividing, they become more and more unstable, which confers a bad prognosis to a patient, because their genetic material is constantly being altered, making the cancer much more difficult to treat.
“In addition to telomere length, we have also identified a molecule called NF-kappaB,” he revealed.
“This molecule is a master regulator of hundreds of different genes, many of which are associated with the control of processes that could result in cancerous changes.
“We’ve shown that by measuring the levels in patients, it allows us to predict whether an individual patient will respond to conventional chemotherapy.
“If they have high levels, they relapse very quickly on conventional therapy.
“The second part of our work is basic tumour cell biology.
“We’re trying to understand what’s driving the malignancy; why do some patients have a very stable disease while others rapidly progress and require chemotherapy.
“It has become increasingly clear that one of the key determinants of disease progression is the ability of the tumour cell to change the micro-environment they exist in. We want to know how.
“People tend to think of cancer as a foreign invader, but it’s not.
“A cancer is essentially yourself, but it has changed subtly from the other cells in your body, which makes it very difficult to identify and to eradicate using your body’s own defence mechanisms.
“In the case of CLL, the disease actually uses the immune system to promote cancer cell survival.
“Work that we have recently published with another colleague, Dr Steve Man, indicates that in the early stages of the disease the immune system probably tries to mount a response to the cancer but once that fails the tumour grows.
“Those same immune system cells are changed by the environment the cancer cells create, making them produce different chemicals which support the growth and the survival of the tumour, making it difficult to treat.
“Our third area of work is to develop novel therapies – we have been involved in the development of a number of new treatments for CLL, including more targeted agents that specifically attack the tumour cell.
“The latest class of drugs we are testing are able to alter the environment tumour cells live and grow in to make them more sensitive to the standard therapies.
“These drugs look set to make a valuable addition to the treatment options for this disease in the near future and we hope that some of them will be trialled here in Cardiff.”
RESEARCH into prostate cancer at the centre focuses on two distinct areas – exosomes and the ongoing STAMPEDE trial.
Although separate areas, both relate to the drive to develop more targeted treatments which respond to individual patients’ disease.
Professor Malcolm Mason, who is leading the research, said: "We want to know why some prostate cancer tumours spread to other parts of the body, when others don’t and we’re also interested in ways we can speed up the development of new drugs.
"When doing drug trials, we rely on conventional measures – we basically give a drug to a patient and if their tumour gets smaller, the drug gets developed further.
"Prostate cancer often spreads to the bones and it can be difficult to assess whether bone metastases are getting smaller.
"Another issue is that trials can take a long time because prostate cancer can be slow growing sometimes – a prostate cancer trial has just been published in The Lancet, which I started putting patients into in the mid 1990s. Somehow we need to make that time shorter.
"There are new biological markers we can use to see whether a patient is responding to treatment – we’re doing this in Cardiff with the financial help of a lot of funders, including Cancer Research Wales, which is putting money into prostate cancer research.
"We are looking at exosomes, which are very tiny – a fraction of the size of a cell – membranes produced by all cells, which have all sorts of things inside them.
"From our point of view, is this a way to measure bio-markers and get a faster indication of whether a patient is responding to treatment?
"We have been able to measure exosomes in the urine of patients and we can see them disappear as they have treatment.
"But there are still technical difficulties in terms of assessing them and we’re still a long way from seeing it in use in a clinic."
STAMPEDE is an international trial designed to assess the safety and effectiveness of hormone therapy in the treatment of prostate cancer. Cardiff is one of the main research centres in the trial – the largest of its kind in the world, involving more than 2,000 patients currently.
Prof Mason added: "My primary role is clinical research and clinical trials – Cardiff is the second highest place in the UK in terms of recruiting patients to STAMPEDE, which is run by the Medical Research Council and funded by Cancer Research UK.
"It compares hormone treatments and hormone therapy plus other drugs, such as chemotherapy, bisphosponates, which prevent bone mass loss and new drugs like abiraterone.
"There will be a lot of information from this trial and some of the first data has already been presented. It’s a very important part of what we’re doing.
RESEARCH into a gene called MBD2 could lead to new treatments for colon cancer, after experts discovered that switching it off prevents tumours from forming.
The breakthrough has been described as a "potential Achilles’ heel" by lead researcher Professor Alan Clarke.
It comes from the work at the Cancer Research UK Centre in Cardiff into how genes and proteins are involved in the formation of cancer.
Prof Clarke said: "The interesting thing about cancer is that one of its primary features is to turn off a number of defensive mechanisms. As the cancer develops, these defensive mechanisms are got around, usually because the genes are switched off or deactivated."
The first breakthrough came with the discovery of the DNMT1 gene, which, when switched off meant that cancers couldn’t develop.
But deactivating DNMT1 also had a significant effect on other bodily functions, meaning it would not make a good target for cancer therapies.
MBD2 belongs to a family of proteins which turn off other genes and research carried out in Cardiff has found that deactivating it prevents colon tumours from developing.
"It’s fantastic and does it with virtually 100% efficiency," Prof Clarke said. "And, taking out MBD2 isn’t that damaging to other tissues and systems – it appears to be tolerated reasonably well.
"Therefore, if we were to have a therapy targeting MBD2, any off-target effects would be limited."
The research team has been examining the impact of MBD2 by creating mice which lack the gene. But many questions remain unanswered.
Prof Clarke said: "We have to show that if you don’t have MBD2 then the likelihood of getting a tumour is much reduced. And we don’t know if you take out MBD2 from a tumour whether it will disappear.
"We’ve been trying to develop a drug that specifically targets MBD2 but, unfortunately, attempts have not been successful because it’s a very difficult protein.
"We think that MBD2 deficiency suppresses tumorigenesis by failing to turn off a number of genes – some these will be important. We’re trying to delve down and find out which of the genes it regulates are important.
"We have a potential Achilles’ heel here to stop tumours forming and we’re also trying to find a drug target.
"We can imagine that this will be useful for patients who have had a tumour and have had therapy but who have a chance of relapsing. But we’re also testing the notion that regulating MBD2 will cause tumours to regress."
Prof Clarke added: "The remarkable thing about the way we treat cancer is that we’re stuck with pretty much ancient technology.
"We mostly use poisons but although we have made progress with virtually all forms of cancer in terms of improving treatment, if we are going to make a huge step change it will have to come from a better understanding of the mechanisms that lead to cancer.
"That will come from a molecular understanding of cancer – if we really understand the molecular basis we can create drugs that make a big difference rather than small, incremental differences."
=============================================================
www.walesonline.co.uk/news/wales-news/2012/01/02/the-cutting-edge-cancer-research-which-could-save-thousands-of-lives-91466-30043704/3/#ixzz1hATTqt83
www.walesonline.co.uk/news/wales-news/2012/01/02/the-cutting-edge-cancer-research-which-could-save-thousands-of-lives-91466-30043704/3/#ixzz1hATTqt83
Hey very cool website!! Man .. Beautiful .. Superb .. I will bookmark your website and take the feeds additionallyà¸KI am satisfied to search out numerous useful info here in the post, we need develop extra techniques on this regard, thank you for sharing. . . . . .
ReplyDeleteSeafolly Women's Pin Up Maillot One Piece Swimwear