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Cancer drug success 'on the rise'
Cancer drug research is entering a new era which will mean more successful drugs for patients, says a charity.
However, Cancer Research UK called for pharmaceutical firms and academics to be more open about those which do not make the grade.
Improved knowledge of cancer's biology means 18% of new drugs, compared with 5% previously - will become standard treatments, said the charity's experts.
Their research was published in the journal Nature Reviews Drug Discovery.
The hunt for cancer drugs is carried out on a massive scale, but there is also a massive failure rate, as promising candidates fall by the wayside in clinical trials.
This costs drug firms and charities such as Cancer Research UK many millions, although scientists can learn lessons even from expensive failures.
Some studies have estimated that, in the past, just 5% of cancer drugs in the pipeline actually end up in the clinic being used day to day.
Data on 974 drugs under development, gathered by Cancer Research UK experts, suggests that 18% of them will prove successful in clinical trials.
It is hoped that many of them will be alternatives to conventional chemotherapy, which can have unpleasant and dangerous side-effects, targeting the mechanisms of cancer cells more directly, with less damage to healthy cells.
Genetic make-up
Dr Ian Walker, the licensing manager at the charity's commercial development arm, said: "This clearly demonstrates the benefits of developing molecularly targeted treatments for cancer - understanding more about the basic biology of cancer is making a real difference to the success rate for new anti-cancer drug development."
The ability to tailor drug choices to the genetic make-up of patients in some cases is also having a benefit.
However, Professor Herbie Newell, also from Cancer Research UK, said that minimising the number of "failures" - and their cost to the industry - would be vital, and this could be helped if researchers and drug companies were more open about what worked, and what did not:
"We strongly believe that both industry and academia must improve the availability of data related to failed as well as successful drug development programmes.
"The sharing of such information can only be beneficial for clinical, scientific and commercial reasons - and will help measure our progress as well as pinpoint areas for improvement."
Bone cancer treatment ineffective, despite promising laboratory data
Ewing sarcoma is the second most common type of primary bone cancer seen in children and young adults. Patients with relapsed or refractory Ewing sarcoma have a poor outcome with conventional therapies. Cytarabine decreases the levels of a certain key protein in Ewing sarcoma cells and has demonstrated preclinical activity against Ewing sarcoma cell lines in the laboratory. Treatment of Ewing sarcoma that relapses is difficult. A new study published in Pediatric Blood and Cancer evaluated a phase II clinical trial of a potential new treatment approach for relapsed Ewing sarcoma using cytarabine.
Ten patients were treated. While one patient's tumour stayed stable in size for approximately 4 months while receiving the drug, none of the ten patients had smaller tumours after treatment with cytarabine. This result is disappointing since laboratory studies indicated that cytarabine might be an effective drug for these patients. In addition, these patients with Ewing sarcoma developed lower blood counts than expected from these doses of cytarabine. The fact that the drug was not found to be effective is yet another example in which laboratory data do not always translate into success in treating patients.
'Cytarabine is not an effective agent for patients with Ewing sarcoma and this drug should be used with caution in heavily pretreated patients with solid tumours due to the significant impact of the drug on blood counts,' says Steven DuBois, co-author of the study. This study demonstrates the difficulties of extending promising therapeutic targets observed in the laboratory to effective treatments in patients. It also emphasises the need for more predictive preclinical models.
Cancer genetic blueprint revealed
Scientists have decoded the complete DNA of a cancer patient and traced her disease to its genetic roots.
The Washington University team identified 10 gene mutations which appeared key to the development of the woman's acute myeloid leukaemia.
Just two of these had been linked to the disease before.
The sequencing technique, described in the journal Nature, could be applied to other cancers and aid the design of targeted drugs.
The researchers took two samples from the woman in her 50s - who later died from the disease - and examined the DNA for differences.
One sample was taken from healthy skin cells, the other from bone marrow tissue made up of cancerous cells.
They found that virtually every cell in the tumour sample had nine of the key mutations.
Like most cancers, acute myeloid leukaemia (AML) - a cancer of blood-forming cells in the bone marrow - arises from mutations that accumulate in people's DNA over the course of their lives.
However, little is known about the precise nature of those changes and how they disrupt biological pathways to cause the uncontrolled cell growth that is the hallmark of cancer.
Previous efforts to decode individual human genomes have looked at common points of DNA variation that may be relevant for disease risk.
In contrast the Washington team, using a gene sequencing technique, were able to sift through the three billion pairs of chemical bases that make up the human genome to pull out the mutations that contributed to the patient's cancer.
True landmark
Geneticist Dr Francis Collins, a former director of the US National Human Genome Research Institute, called the study a "true landmark in cancer research".
He said: "In the past, cancer researchers have been 'looking under the lamp-post' to find the causes of malignancy - but now the team from Washington University has lit up the whole street.
"This achievement ushers in a new era of comprehensive understanding of the fundamental nature of cancer, and offers great promise for the development of powerful new approaches to diagnosis, prevention and treatment."
Three of the newly-discovered mutations were in genes that normally suppress tumour growth, and four were in genes linked to the spread of cancer.
The other appears to affect the transport of drugs into the cells, possibly fuelling resistance to cancer therapy.
The researchers are still looking for other gene mutations which may also play a part.
They also examined tumour samples from another 187 AML patients, but found none had any of the eight new mutations.
Lead researcher Dr Richard Wilson said: "This suggests that there is a tremendous amount of genetic diversity in cancer, even in this one disease.
"There are probably many, many ways to mutate a small number of genes to get the same result, and we're only looking at the tip of the iceberg in terms of identifying the combinations of genetic mutations that can lead to AML."
The researchers suspect that the mutations occurred one after another, with each pushing the cell closer to malignancy.
Kat Arney, of the charity Cancer Research UK, said: "This is a very important piece of research, not only for our understanding of leukaemia but for many other types of cancer.
"Thanks to advances in technology it is now possible to unlock the genetic secrets within cancer cells, which will be the key to better diagnostic tools and treatments in the future."
Ken Campbell, of Leukaemia Research said: "Although it is very early days, it is realistic to think that these findings could lead to new treatments.
"Its wider application to other cancers may be limited though - the technique is particularly valuable for blood cancers in which the chromosome changes are usually simpler than in solid tumours at the time of diagnosis."
Gene 'roadmap' for lung cancers
The most complete survey yet of the genes which go wrong when lung cancer takes hold has been carried out by US researchers.
The findings, which doubled the number of genes linked to a common form of the disease, will guide researchers in the hunt for new treatments.
A UK specialist said some of the genes listed by the research were already being examined further by scientists.
Fewer than 10% of UK lung cancer patients survive more than five years.
Like most cancers, the development of lung cancer is due to changes, or mutations, in the DNA of patients accumulated over many years.
The scientists looked at samples of lung adenocarcinoma donated by 188 patients from across the US, then worked through a catalogue of 623 "suspect" genes, many implicated in other cancers, comparing them in detail to the same genes in healthy tissue from the same patient.
They found 1,000 different mutations across all the samples, but found the same 26 mutations cropping up again and again - most of which had never been linked to lung cancer before.
These are likely to be explored in more detail to find out what role they play in the development and spread of the disease, and whether they might be blocked by new treatments.
Dr Alan Guttmacher, from the National Human Genome Research Institute, said: "By harnessing the power of genomic research, this pioneering work has painted the clearest and most complete portrait yet of lung cancer's molecular complexities."
Smoking damage
The research also looked at the differences between tumours in smokers or former smokers - who make up 90% of lung cancer patients, and those in non-smokers.
They found a far higher rate of mutations in the tumours taken from smokers.
Although the researchers found clues which point strongly to the importance of particular chemical processes in lung cancer, none of the findings will produce new treatments immediately.
Dr Richard Gibbs, from the Baylor College of Medicine in Texas, and one of the co-authors of the research, said: "Clearly, much still remains to be discovered.
"We have just begun to realise the tremendous potential of large-scale genomic studies to unravel the many mysteries of cancer."
Professor Michael Seckl, head of Cancer Research UK's Lung Cancer Group at Imperial College London, said that the research was "exciting", both confirming that existing research was heading in the right direction, and throwing up possibilities for new projects.
He said: "It's highly useful but it will take some time to be fully translated into treatments that can help patients.
"Some people, including ourselves, are already working on some of these areas, and this research is like the icing on the cake as far as confirming that we are doing the right thing."
Breast cancer 'kills more poor'
Breast cancer is more likely to kill poor women than their more affluent counterparts, research shows.
A study of breast cancer patients in England and Wales diagnosed between 1986 and 1999 found overall long-term survival rates are improving.
However, survival rates one year after diagnosis were worse among poor women than those who were more affluent.
And the British Journal of Cancer study found this "deprivation gap" doubled five years after diagnosis.
The study, which looked at more than 380,000 women, found that even after adjustijng for other causes of death, the five-year survival rate was about 6% higher for affluent women.
The figures are part of a detailed analysis of survival rates for the 20 most common forms of cancer.
The researchers found that one-year survival rates tended to be higher among affluent women across a range of cancers.
However, breast cancer was the only form of the disease for which this deprivation gap continued to widen years after diagnosis.
Lead researcher Professor Michel Coleman, an epidemiologist for Cancer Research UK, said women from poor backgrounds might be less likely to access radiotherapy or drug treatment.
Others said the key could be that patients living in deprived areas were more likely to be diagnosed at a late stage, or to have other life-threatening diseases.
Improvements
Dr Sarah Cant, of the charity Breakthrough Breast Cancer, said there had been significant improvements in access to services and treatments since the 2000 Cancer Plan which would not be be reflected in the study.
However, she said: "The inequalities in breast cancer survival between richer and poorer women that have been identified are of great concern.
"It is vital to continue to investigate the exact causes of any inequalities so appropriate measures to tackle them can be taken."
Professor Mike Richards, National Cancer Director for England, said there tended to be a difference of opinion between clinicians and epidemiologists about the reasons for a deprivation gap.
He said: "In general clinicians were likely to attribute the deprivation gap in survival mainly to the fact that people from poorer backgrounds had other diseases as well as cancer.
"By contrast statisticians put more emphasis on late diagnosis in deprived groups as a cause for poorer survival.
"These differences of opinion highlight the need for high quality information on the details of cancer staging and additional diseases to be collected by clinical teams and made available to the cancer registries."
For most cancers survival up to 10 years has improved significantly between those diagnosed in the mid 1980s and the late 1990s.
But there was almost no change in survival for lung, pancreatic, cervical and bladder cancer.
Cancer: Getting the big picture
Genetic profiling is providing a new slant on cancer. In the July issue of Genome Biology, researchers in the Informatics Program (CHIP) at Children's Hospital Boston showed that cancers can be divided into three distinct groups, which could provide new insight into patient prognoses and possibly alter treatment decisions.
Traditionally, scientists studying cancer have devoted a great deal of attention to individual genes, boosting or suppressing their activity in the laboratory to tease out their respective roles in tumour formation. The CHIP researchers opted for a more holistic approach, systematically comparing the genetic profiles of a broad range of cancers to those seen during embryonic development, which allowed them to sort gene expression patterns in cancer along a continuum.
"Basically, there are three major groups in this continuum," says Kamila Naxerova, first author on the study and a graduate student working with CHIP director and senior author Isaac Kohane, MD, PhD. "The first has stem-cell-like and proliferative expression patterns similar to early development; another group expresses many genes linked to inflammation and is reminiscent of late development. The third is intermediate, falling somewhere between the other two."
The map describes three groups of human cancers, showing similarities in gene expression between different tumour-types and a range of developmental processes. Cancers in group 1 reactivate many early developmental genes; those in group 3 have gene activity patterns resembling late development. Red indicates a strong correspondence between gene expression in the cancer versus that in development, and green a weak relationship; black is intermediate.
Such "developmental timing" of tumours could potentially provide important information about a cancer's prognosis, adds Naxerova. Cancers with active genes characteristic of early development are generally undifferentiated and grow aggressively; cancers in the late developmental group are more indolent, with lower growth rates.
Naxerova and colleagues were surprised at some of the cancers that wound up in the same category. For instance, both adenocarcinoma - the most common form of lung cancer - and Wilms' tumour - a type of paediatric kidney cancer - landed in the early developmental group.
"It's not what I would have expected, since these tumours arise under very different circumstances and are associated with different DNA alterations," says Naxerova. "But grouping cancers in this developmental context could provide a different therapeutic strategy."
In other words, as unlikely as it seems, drugs effective against lung cancer could well be used to treat kidney tumours in children.
"We're trying to capture a tumour's macroscopic properties," says Naxerova. "We're really going after the big picture here."
Positive thinkers 'avoid cancer'
Women who have a positive outlook may decrease their chances of developing breast cancer, say Israeli researchers.
The small study, published in the BioMed Central journal, also found that getting divorced, or being bereaved could increase the risk.
But the researchers admitted that women were questioned after their diagnosis, which might significantly change their outlook on life.
UK experts said it was hard to compare different women's emotional stresses.
The role of mental outlook on cancer remains controversial, with some studies suggesting that it might play a role.
Meanwhile, others have found no significant effect, either on the likelihood of developing the illness in the first place, or on your chances of surviving it.
The latest study looked at 255 women with breast cancer and compared their answers in a questionnaire on mental outlook and life events with 367 healthy control subjects.
They found that a generally positive outlook appeared to reduce the chance of breast cancer by a quarter.
In addition, exposure to one or more of the traumatic "life events" such as loss of a parent or a spouse increased the risk by more than 60%.
Lead researcher Dr Ronit Peled, from Ben-Gurion University, said that women who had been exposed to a number of negative events should be considered an "at-risk" group for breast cancer.
"We can carefully say that experiencing more than one severe and/or moderate life event is a risk factor for breast cancer among young women.
"On the other hand, a general feeling of happiness and optimism can play a protective role."
'Complex disease'
But Dr Sarah Cant, from Breakthrough Breast Cancer, maintained that there was no clear evidence that positive or negative experiences could affect breast cancer risk.
"Emotional stress is highly subjective and is difficult to measure accurately.
"Women in this study were interviewed after breast cancer was diagnosed when they may be more likely to recall feeling depression and anxiety.
"The researchers also didn't account for other factors known to affect breast cancer risk such as family history or weight.
"Breast cancer is a complex disease and there is unlikely to be one single cause."
Turned-Off cannabinoid receptor turns on colorectal tumour growth
New preclinical research shows that cannabinoid cell surface receptor CB1 plays a tumour-suppressing role in human colorectal cancer, scientists report in the Aug. 1 edition of the journal Cancer Research.
CB1 is well-established for relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signalling molecules. It now may serve as a new path for cancer prevention or treatment.
"We've found that CB1 expression is lost in most colorectal cancers, and when that happens a cancer-promoting protein is free to inhibit cell death," said senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president of The University of Texas M. D. Anderson Cancer Center.
DuBois and collaborators from Vanderbilt-Ingram Cancer Center also show that CB1 expression can be restored with an existing drug, decitabine. They found that mice prone to developing intestinal tumours that also have functioning CB1 receptors develop fewer and smaller tumours when treated with a drug that mimics a cannabinoid receptor ligand. Ligands are molecules that function by binding to specific receptors. Agonists are synthetic molecules that mimic the action of a natural molecule.
"Potential application of cannabinoids as anti-tumour drugs is an exciting prospect, because cannabinoid agonists are being evaluated now to treat the side-effects of chemotherapy and radiation therapy," DuBois said. "Turning CB1 back on and then treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention."
Cannabinoids are a group of ligands that serve a variety of cell-signalling roles. Some are produced by the body internally (endocannabinoids). External cannabinoids include manmade versions and those present in plants, most famously the active ingredient in marijuana (THC).
Receptor shutdown by methylation
Endocannabinoid signalling is important to the normal functioning of the digestive system and has been shown to protect the colon against inflammation. Since chronic inflammation is a known risk factor for colorectal cancer, the researchers decided to look into the role of cannabinoid receptors in a mouse model of colon cancer.
"People have looked at cannabinoids in cancer earlier, mainly in cell culture experiments," DuBois said. "The molecular mechanisms for loss of the receptor and its effect on cancer have not been previously shown."
First, the team found that CB1 was largely absent in 18 of 19 human tumour specimens and in 9 of 10 colorectal cancer cell lines. Further experimentation showed that the gene that encodes the CB1 protein was not damaged, but shut down chemically by the attachment of methyl groups - a carbon atom surrounded by three hydrogen atoms - to the gene encoding CB1.
Treating cell lines with decitabine, a demethylating agent approved for some types of leukaemia, removed the methyl groups, restoring gene expression in 7 of 8 cell lines and full expression of CB1 protein in three lines.
Next, the group found that deletion of the CB1 gene in a strain of mice that spontaneously develops precancerous polyps resulted in a 2.5-to-3.8-fold increase in the number of polyps and a 10-fold increase in the number of large growths, those most likely to develop into cancer.
Treating mice that had the CB1 receptor with an endocannabinoid agonist resulted in a decline in polyps ranging from 16.7 percent to 50 percent. The reduction was greater for larger polyps.
CB1 thwarts survivin, a protein that protects cancer
Cannabinoids previously had been shown to kill cancer cells in lab experiments by inducing apoptosis - programmed cell death. The team confirmed the role of CB1 in apoptosis, showing that tumour cells with high CB1 expression were sensitive to apoptosis when treated by a cannabinoid agonist. Cell lines with silenced CB1 resisted cell death.
A series of experiments showed that CB1 increases cancer cell death by stifling a protein called survivin. Survivin is overexpressed in nearly every human tumour but is barely detectable in normal tissue, DuBois noted. Over expression of survivin is associated with poor outcome and reduced apoptosis in colorectal cancer patients. The researchers pinpointed a cell signalling pathway by which activated CB1 cuts down survivin.
"Just increasing the levels of cannabinoids to treat colorectal cancer won't work if the CB1 receptor is not present," DuBois said. This suggests that treating first with a demethylating agent, such as decitabine, to reactivate CB1 in the tumour and following up with a cannabinoid might be an effective attack on colorectal cancer.
Scarcity of CB1 also is associated with Huntington's disease, Alzheimer's disease and multiple sclerosis. Further investigation, the researchers note, is needed to define its role in those diseases and other types of cancer. The team also analysed the other main cannabinoid receptor, CB2, and found no role for it in colorectal cancer.
They also treated the mice with a CB1 antagonist, a compound that binds to the receptor but does not activate it. Mice with CB1 blocked in this manner also showed an increase in the number and size of polyps. A CB1 antagonist called rimonabant is currently marketed overseas for weight loss. The researchers note that a patient's risk for colorectal cancer should be assessed when use of such drugs is being considered.
Australian and New Zealand Researchers Identify Genes Which Help Immune System to Fight Cancer
Today marks the first day of the Australia and New Zealand joint scientific meeting for the Medical Oncology Group of Australia and the Faculty of Radiation Oncology, held in Christchurch NZ.
Cancer specialists from Australasia today heard some of the latest ground breaking research in tumour biology. A selection of presentations highlighted some of the giant strides forward that are being made in understanding how tumours metastasise (spread to other parts of the body).
Researchers analysed gene signatures from colon cancer cells to see which genes predicted for a bad outcome. Dr Mik Black, Biochemisty Scientist at Otago University NZ, presented the unexpected finding that bowel cancer tumours that grow quickly appeared to have a better outcome than less aggressive tumours.
This is the opposite to what is seen in most tumours, eg breast cancers that have a high proliferation rate (cells grow very quickly) have a much worse outcome than those with a low proliferation rate.
He discussed the work by Dr Ahmed Anjomshoaa, shortly to be published in the British Journal of Cancer, which demonstrated that bowel tumours with high proliferation rates were associated with a better outcome independent of whether or not they had chemotherapy.
This suggests that chemotherapy may be more effective in slow growing cancer colon tumours. Dr Black pointed out that gastric (stomach) cancer had a similar profile and he raised the question as to whether or not the tumours with higher proliferation rate stimulate a more aggressive immune response.
He hypothesised that tumours with a high proliferation rate may be sufficiently different from normal colon (bowel) cells for the immune system to recognise them and attack them thus retarding cancer cell growth.
This was borne out by his finding that the myc gene was overexpressed in tumours with a high proliferation rate and that the myc gene was known to be associated with immune system activation.
Stay posted to Virtual Medical Centre for more breaking news from the conference.
Vitamin C 'slows cancer growth'
An injection of a high dose of vitamin C may be able to hold back the advance of cancers, US scientists claim.
The vitamin may start a destructive chain reaction within the cancer cell, they add.
The jab halved the size of brain, ovarian and pancreatic tumours in mice, reported the journal Proceedings of the National Academy of Sciences.
However, Cancer Research UK said other studies suggested large vitamin C doses may interfere with cancer treatment.
Earlier research by the team at the National Institutes of Health in Maryland had suggested that the vitamin, also called ascorbate, could kill cancer cells in the laboratory.
After these successful tests in mice, they are now suggesting that the treatment be considered for human use at similar levels.
The dose they employed - up to four grams per kilo of bodyweight - was far greater than any that could be achieved using diet or vitamin pills, as the digestive system does not absorb more than a fixed amount taken orally.
The mice were bred to have malfunctioning immune systems, then injected with human cancer cells, which as a result, grew quickly into large tumours. The vitamin was then injected into their abdominal cavity.
Tumour growth and weight fell by between 41% and 53%, and while in untreated mice, the disease spread rapidly to involve other body parts, no such spread was seen in the vitamin C-treated animals.
The researchers wrote: "These pre-clinical data provide the first firm basis for advancing pharmacologic ascorbate in cancer treatment in humans."
Peroxide bomb
The treatment works because a tumour cell is chemically different to a healthy cell.
The vitamin C reacts with this chemical make-up, producing enough hydrogen peroxide to kill the cell, while leaving healthy cells unscathed.
However, Dr Alison Ross, from Cancer Research UK said that much more work would have to be done to see if vitamin C could be a viable treatment.
"This is encouraging work but it's at a very early stage because it involves cells grown in the lab and mice.
"There is currently no evidence from clinical trials in humans that injecting or consuming vitamin C is an effective way to treat cancer.
"Some research even suggests that high doses of antioxidants can make cancer treatment less effective, reducing the benefits of radiotherapy and chemotherapy."
New HPV infections will plummet by 2010
The number of new human papillomavirus (HPV) infections in Australian females is expected to more than halve by 2010 and fall by 92 per cent by 2050, thanks to extensive HPV vaccination, according to a new study by Cancer Council.
The study, published in the International Journal of Cancer, looks at the predicted impact of the National HPV Vaccination Program in Australia, which began in April 2007. HPV immunisation has the potential to prevent up to 70 per cent of cervical cancers.
“We expect to see a very fast reduction in the number of new HPV infections, largely due to the high school vaccination program, which we estimate has achieved high coverage of just over 80 percent of 12 to 13 year-old girls,” says Dr Karen Canfell, from Cancer Council’s Research Division in NSW and lead author of the report.
"But we cannot afford to rest on our laurels. This reduction will only occur if we maintain this high vaccination coverage amongst younger age groups, as it will provide immunity against HPV before girls are exposed to the virus," she said.
Co-author Dr Julia Brotherton, from the National Centre for Immunisation Research and Surveillance, agrees saying: “Parents of girls in Years 7 to 10 need to take the opportunity for their daughters to be vaccinated now, as the free vaccination program for all girls only runs until 2009. This could save your daughter’s life.”
According to Dr Canfell it will still take some time for the reduction in HPV to translate to a significant decrease in cervical cancer. “Cervical cancer is a slow developer, but we do know that HPV immunisation has the potential to prevent a large proportion of cervical cancers.
“While this is all very positive news, we must remind all women to continue being screened through regular Pap testing, even those who have been vaccinated,” added Dr Canfell. “The HPV vaccine doesn’t protect against all types of cancer-causing HPV, so regular screening is absolutely essential to detect abnormal cell changes that can be treated before cancer develops.”
Cancer Council recommends that all women aged 18-70 who have ever had sex should have regular Pap tests, as per the National Medical Health and Research Guidelines which recommend testing every two years.
Barrett's oesophagus eliminated when treated with ablation procedure
One in 10 Americans experiences heartburn at least once a week, and many dismiss the malady as a mere annoyance, choosing to swallow antacids and get on with their lives.
But what they don't know can hurt them. Left untreated, the condition can lead to Barrett's oesophagus, which in turn can put patients at risk for oesophageal cancer, one of the most deadly forms of cancer.
Now a multi-center clinical trial led by David E. Fleischer, M.D., Gastroenterology, Mayo Clinic in Arizona, has revealed promising results in treatment of Barrett's oesophagus. The study, released today by BARRX Medical, Inc., finds that the 98.4 percent of patients with Barrett's oesophagus were free of the disease 2 and 1/2 years later following non-surgical, endoscopic treatment with radiofrequency ablation.
In the procedure, the physician can ablate, or zap, abnormal tissue within the oesophagus. Called the HALO ablation system, two components are used to remove diseased tissue — one treats large, circumferential areas of the oesophagus, and the other component targets focal, non-circumferential disease.
Results were published online this month in Gastrointestinal Endoscopy, a leading scientific publication for gastrointestinal physicians and researchers.
In the clinical trial, eight U.S. centres enrolled 70 patients having intestinal metaplasia, which is the earliest stage of Barrett's oesophagus. Because of an elevated risk for developing oesophageal cancer, patients with the disorder generally submit to a lifetime of endoscopic examinations (surveillance) to detect potential progression to more advanced stages of the disease — or cancer. The purpose of the study was to find out if this treatment could eliminate Barrett's and possibly be an alternative to surveillance.
After treatment, patients in the trial were monitored for 2 and 1/2 years through regular endoscopic examinations to confirm if all of the diseased areas were eliminated. At the final evaluation, 98.4 percent of patients had achieved a complete response to therapy and had no remaining disease.
"This study represents an important step in understanding the best way to manage patients with Barrett's oesophagus at the earliest phase of the disease and demonstrates that intestinal metaplasia can be eliminated," says Dr. Fleischer He went on to emphasise two points: (1) Since the majority of patients who have intestinal metaplasia do not go on to develop oesophageal cancer, most guidelines recommend surveillance for the first phase of Barrett's, and (2) Elimination of Barrett's does not eliminate acid reflux, which led to Barrett's, so it must continue to be treated. He also added that ongoing trials continue to add to the body of knowledge about the ablation technique and its potential to reduce the risk of progression of the disease.
Beating depression for cancer patients
A new treatment programme for cancer patients with clinical depression can significantly boost their quality of life according to new research published in the Lancet today.
Cancer Research UK scientists devised the treatment programme which offers patients one-to-one sessions with specially trained cancer nurses to help them manage their depression more effectively.
They found that, after three months of receiving the new treatment, almost 20 per cent fewer patients were depressed compared with patients who received standard NHS treatment. The difference was still evident after one year.
The study recruited 200 cancer patients with clinical depression and compared the new strategy – "Depression Care for People with Cancer" – with the standard NHS treatment.
Half were given standard care for depression either from their GP or hospital specialist. The other half received the special programme which entailed sessions on: understanding depression and the effects of antidepressants; problem-solving therapy to help patients overcome feelings of helplessness; liaison with oncologist and GP to collaborate in treatment of depression; monthly monitoring of progress by telephone and providing optional "booster" sessions.
After three months, the patients who were treated in this way found there was an improvement in anxiety and fatigue as well as depression.
Professor Michael Sharpe, from the Psychological Medicine Research group at the University of Edinburgh which carried out the study, said: "Ten per cent of cancer patients experience clinical depression and, unfortunately, it is not always adequately treated. This new treatment could substantially improve the way we manage depression in people with cancer and also in people with other serious medical conditions.
"This is the first time that this type of depression treatment has been evaluated in cancer patients and the results are very encouraging."
Cancer Research UK, which funded the study, has recently awarded Professor Sharpe's research team more than L4 million to continue their work in finding better ways to treat depression and other symptoms in cancer patients.
Dr Lesley Walker, Cancer Research UK's director of cancer information, said: "As well as finding ways to prevent and treat cancer, the charity is committed to improving the quality of life for people who are living with the disease."
US cancer boss in mobiles warning
The director of a leading US cancer research institute has sent a memo to thousands of staff warning of possible higher risks from mobile phone use.
Ronald Herberman, of the University of Pittsburgh Cancer Institute, said users should not wait for definitive studies on the risk and should take action now.
He said children should use mobiles in emergencies only and adults should try to keep the phone away from the head.
No major academic study has confirmed a link to higher brain-tumour risks.
Electromagnetic fields
Dr Herberman said his warning was based on early findings from unpublished data.
"We shouldn't wait for a definitive study to come out, but err on the side of being safe rather than sorry later," he says.
"I am convinced that there are sufficient data to warrant issuing an advisory to share some precautionary advice on cell phone use," the memo says.
Dr Herberman's warning to 3,000 staff says children should be protected as their brains are still developing.
He lists tips including switching sides regularly while talking on mobiles.
A major six-year research study in the UK said last year that there were no short-term adverse effects to brain and cell function from mobile phone use.
However, the UK Mobile Telecommunications and Health Research Programme said there was a "hint" of a higher cancer risk in the long term and that its research would look into the effects over a 10-year period.
Programme chairman Professor Lawrie Challis said: "We can't rule out the possibility at this stage that cancer could appear in a few years' time."
An earlier UK report said in 2005 that mobile phone use by children should be limited as a precaution - and that under-eights should not use them at all.
Mobile phones emit radio signals and electromagnetic fields that can penetrate the human brain, and some campaigners fear that this could seriously damage human health.
A US analysis by the University of Utah this year of thousands of brain tumour patients found no increased risk as a result of mobile use, but added that the effects from long-term use "awaits confirmation by future studies".
Research reported in 2006 by the British arm of an international project called Interphone concluded that mobile phone use did not lead to a greater risk of brain tumour.
Recent Danish and French studies also found no increased risk of cancer.
But a study of 500 Israelis found this year that heavy mobile phone use might be linked to an increased risk of cancer of the salivary gland.
New oral angiogenesis inhibitor offers potential nontoxic therapy for a wide range of cancers
The first oral, broad-spectrum angiogenesis inhibitor, specially formulated through nanotechnology, shows promising anticancer results in mice, report researchers from Children's Hospital Boston. Findings were published online on June 29 by the journal Nature Biotechnology.
Because it is nontoxic and can be taken orally, the drug, called Lodamin, may be useful as a preventive therapy for patients at high risk for cancer or as a chronic maintenance therapy for a variety of cancers, preventing tumours from forming or recurring by blocking the growth of blood vessels to feed them. Lodamin may also be useful in other diseases that involve aberrant blood-vessel growth, such as age-related macular degenera
Developed by Ofra Benny, PhD, in the Children's laboratory of the late Judah Folkman, MD, Lodamin is a novel slow-release reformulation of TNP-470, a drug developed nearly two decades ago by Donald Ingber, MD, PhD, then a fellow in Folkman's lab, and one of the first angiogenesis inhibitors to undergo clinical testing. In clinical trials, TNP-470 suppressed a surprisingly wide range of cancers, including metastatic cancers, and produced a few complete remissions. Trials were suspended in the 1990s because of neurologic side effects that occasionally occurred at high doses, but it remains one of the broadest-spectrum angiogenesis inhibitors known.
Lodamin appears to retain TNP-470's potency and broad spectrum of activity, but with no detectable neurotoxicity and greatly enhanced oral availability. While a number of angiogenesis inhibitors, such as Avastin, are now commercially available, most target only single angiogenic factors, such as VEGF, and they are approved only for a small number of specific cancers. In contrast, Lodamin prevented capillary growth in response to every angiogenic stimulus tested. Moreover, in mouse models, Lodamin reduced liver metastases, a fatal complication of many cancers for which there is no good treatment.
"The success of TNP-470 in Phase I and II clinical trials opened up anti-angiogenesis as an entirely new modality of cancer therapy, along with conventional chemotherapy, radiotherapy and surgical approaches," says Ingber, now co-interim director of the Vascular Biology Program at Children's.
TNP-470 was first reformulated several years ago by Ronit Satchi-Fainaro, PhD, a postdoctoral fellow in Folkman's lab, who attached a large polymer to prevent it from crossing the blood-brain barrier (Cancer Cell, March 2005). That formulation, Caplostatin, has no neurotoxicity and is being developed for clinical trials. However, it must be given intravenously.
Benny took another approach, attaching two short polymers (PEG and PLA) to TNP-470. Experimenting with polymers of different lengths, she found a combination that formed stable, "pom-pom"-shaped nanoparticles known as polymeric micelles, with TNP-470 at the core. The polymers (both FDA-approved and widely used commercially) protect TNP-470 from the stomach's acidic environment, allowing it to be absorbed intact when taken orally. The micelles reach the tumour, react with water and break down, slowly releasing the drug.
Tested in mice, Lodamin had a significantly increased half-life, selectively accumulated in tumour tissue, blocked angiogenesis, and significantly inhibited primary tumour growth in mouse models of melanoma and lung cancer, with no apparent side effects when used at effective doses. Subsequent tests suggest that Lodamin retains TNP-470's unusually broad spectrum of activity. "I had never expected such a strong effect on these aggressive tumour models," Benny says.
Notably, Lodamin accumulated in the liver without causing toxicity, preventing liver metastases and prolonging survival. "This was one of the most surprising things I saw," says Benny. "When I looked at the livers of the mice, the treated group was almost clean. In the control group you couldn't recognize the livers -- they were a mass of tumours."
TNP-470 itself has an interesting history. It was derived from fumagillin, a mould with strong anti-angiogenic effects that Ingber discovered accidentally while culturing endothelial cells (the cells that line blood vessels). Ingber noticed that in certain dishes -- those contaminated with the mould -- the cells changed their shape by rounding, a behaviour that inhibits capillary cell growth. Ingber cultured the fungus, disregarding lab policy, which called for contaminated culture to be discarded immediately. He and Folkman later developed TNP-470, a synthetic analogue of fumagillin, with the help of Takeda Chemical Industries in Japan (Nature, December 1990). It has shown activity against dozens of tumour types, though its mechanism of action is only partly known.
"It's been an evolution," says Benny, "from fumagillin to TNP-470 to Caplostatin to Lodamin."
Reducing cancer patients' swollen side effect of treatment
It is a side effect of cancer treatment often hidden away and rarely spoken about, but secondary lymphoedema* (or the chronic, often painful swelling of body parts) can have a debilitating impact on the lives of the 8000 Australians diagnosed with the condition each year.
Today, National Breast and Ovarian Cancer Centre is launching two initiatives to reduce the incidence and improve the treatment and support of all cancer patients affected by lymphoedema.
It is estimated that approximately 20 per cent of survivors from melanoma, breast, gynaecological or prostate cancer will experience secondary lymphoedema. Yet the condition can be effectively managed with early intervention and treatment.
“The swelling associated with lymphoedema can make everyday activities such as walking or writing painful and very difficult,” said Dr Helen Zorbas, National Breast and Ovarian Cancer Centre Director.
“People with lymphoedema can also experience embarrassment about the way they look, which can significantly impact on their body image and relationships with others. With more and more Australians surviving cancer, improving the quality of life of cancer survivors is becoming increasingly important,” said Dr Zorbas.
Minister for Health and Ageing Nicola Roxon said “Cancer is one of the biggest challenges any of us can face in life. We want to do all we can not only to help people access the most effective treatments, but also to support them in managing any difficult side effects.”
Despite the prevalence of the condition, there has previously been limited evidence-based information to support people affected by secondary lymphoedema and to guide health professionals involved in the diagnosis, treatment and management of the condition.
In response, National Breast and Ovarian Cancer Centre has developed a range of secondary lymphoedema resources based on the best available Australian and international evidence, funded by an Australian Government grant. The resources include:
a guide for health professionals on the management of secondary lymphoedema
workshop training modules for health professionals and Indigenous health workers, and
comprehensive information for people either at risk of or diagnosed with secondary lymphoedema. The consumer resources have been translated into Arabic, Chinese, Greek, Italian and Vietnamese and a culturally appropriate version is available for Indigenous Australians.
Additionally, National Breast and Ovarian Cancer Centre is today releasing clinical practice recommendations for the use of a surgical technique shown to substantially reduce the incidence of lymphoedema in breast cancer survivors. The recommendations have been endorsed by the peak national organisation for Australians affected by breast cancer, Breast Cancer Network Australia.
The surgical technique known as ‘sentinel node biopsy’ is a less invasive procedure than has been traditionally used to determine whether breast cancer cells have spread to the lymph nodes under the armpit (see attached fact sheet for more details about the procedure).
“We are pleased to be able to provide guidance on two fronts to both decrease the incidence and improve the management of secondary lymphoedema,” said Dr Zorbas.
Skin cancer fear 'may harm bones'
Worries over skin cancer mean that some people are shunning the sun altogether - which could endanger their health, a poll has found.
The National Osteoporosis Society (NOS) says lack of vitamin D - part-made by being in the sun - could raise the chances of brittle bone disease.
It advised having lunch outside, gardening or hanging out the washing.
A Cancer Research UK spokesman agreed, but said enough vitamin D could be made long before the first signs of sunburn.
Skin cancer rates have soared in recent years, and health campaigners increasingly urge people to limit the amount of time they spend in direct sunlight without the protection of sunscreen or clothing.
However, the NOS said its survey of more than 2,600 people in June revealed that many believe there is no such thing as safe sun exposure.
Three-quarters of those questioned said that sunscreen should always be applied before going out in the sun.
However, the NOS said that not getting at least 15 to 20 minutes of sunlight on the skin every day could be harmful.
Light falling on the skin produces vitamin D, which is important for bone strength, and studies suggest that low levels of this could raise the risk of osteoporosis, which affects half of all women and a fifth of men over the age of 50.
Outdoors only
Professor Roger Francis, from the NOS Medical Board, said its finding showed the success of public health messages on skin cancer.
"We are not advocating spending lengthy periods in the sun, as too much sun causes skin ageing and melanoma.
"Furthermore, staying in the sun too long means that the body breaks down surplus vitamin D shortly after it is produced.
"Lying on the beach for two weeks will not top up levels for the rest of the year."
He urged people to get out into the light every day - even during cloudy days - to get enough vitamin D to last through the winter.
Simply sitting by a closed window or in a conservatory was not enough, he said, as this did not produce vitamin D.
Caroline Cerny, from Cancer Research UK, which runs its SunSmart campaign to warn people about skin cancer, said the key was a sensible approach.
"The amount of time in the sun required to make enough vitamin D changes from person to person and depends on things like skin type, time of day, time of year, and where you are in the world .
"We all need a bit of sunshine in our lives, but it's important to remember that the amount of sun needed to make enough vitamin D is always less than the amounts that cause reddening of the skin or sunburn."
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Breast Cancer
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Cancer
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Cancer (medicine), any of more than 100 diseases characterized by excessive, uncontrolled growth of abnormal cells, which invade and destroy other tissues. Cancer develops in almost any organ or tissue of the body, but certain types of cancer are more lethal than others. Cancer is the leading cause of death in Canada and second only to heart disease in the United States.
Each year, more than 1.2 million Americans and 132,000 Canadians are diagnosed with cancer, and more than 1,700 people die from cancer each day in the United States and Canada. For reasons not well understood, cancer rates vary by gender, race, and geographic region. For instance, more males have cancer than females, and African Americans are more likely to develop cancer than persons of any other racial and ethnic group in North America. Cancer rates also vary globally—residents of the United States, for example, are nearly three times as likely to develop cancer than are residents of Egypt.
Just 50 years ago a cancer diagnosis carried little hope for survival because doctors understood little about the disease and how to control it. Today 60 percent of all Americans diagnosed with cancer live longer than five years. While it is difficult to claim that a cancer patient is disease free, long-term survival significantly improves if the patient survives five years. The National Cancer Institute of the United States (NCI) estimates that as many as 8.4 million Americans are living with cancer or have been cured of the disease thanks largely to advances in detecting cancers earlier. The sooner cancer is found and treated, the better a patient’s chance for survival. In addition, advances in the fundamental understanding of how cancer develops have reduced deaths caused by certain cancers and hold promise for new and better treatments.
Epithelial tissue forms a protective layer of cells that covers organ surfaces and lines body cavities. Shown here is a layer of simple squamous (scaly) epithelium under magnification. Cancers that arise in epithelial tissues, called carcinomas, account for approximately 90 percent of all human cancers.
Connective tissues include bone, cartilage, fat, ligaments, and tendons. These tissues support and connect parts of the body. The structure varies depending on the purpose of the tissue. The diagonal red band in this image shows elastin fiber, which allows connective tissue to spring back into shape following deformation. Cancers called sarcomas orginate in connective tissues. Rare, sarcomas constitute only about 2 percent of all human cancers. Sarcomas are elusive in their early stages. They may arise deep within connective tissues, making them more likely to spread to distant parts of the body before they are detected.
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Next: HOW CANCER DEVELOPS
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