Scientists have developed a gene test which predicts how well chemotherapy will work in cancer patients.

Starting with 829 genes in breast cancer cells, the team whittled down the possibilities to six genes which had an impact on whether a drug worked.

They then showed that these genes could be used to predict the effectiveness of a drug called paclitaxel in patients.

It is hoped the approach, reported in The Lancet Oncology, can be replicated for other cancers and treatments.

The international project, including researchers from Cancer Research UK’s London Research Institute, opens the way for breast cancer treatment to be targeted to those who will benefit the most.

To find which genes, if missing or faulty, could prevent the drug from working, they deleted them one by one from cancer cells in the laboratory.

They eventually highlighted the six genes which if absent or not working prevent paclitaxel from properly killing breast cancer cells.

Spare treatment

More than 45,500 women are diagnosed with breast cancer in the UK each year – and it is estimated that around 15% of these women will be prescribed paclitaxel.

The researchers estimate they could potentially spare half of the patients currently receiving this drug from treatment which would not be effective.

Study leader, Dr Charles Swanton, head of translational cancer therapeutics at the Institute, said one of the great challenges in cancer medicine is determining which patients will benefit from particular cancer drugs, which are in themselves toxic and carry severe side effects.

“Our research shows it is now possible to rapidly pinpoint genes which prevent cancer cells from being destroyed by anti-cancer drugs and use these same genes to predict which patients will benefit from specific types of treatment.”

Further studies will now be done to see if the technique can be developed into a simple diagnostic test to be given to patients to help inform doctors about whether or not to prescribe paclitaxel.

He said the challenge will be to apply these methods to other drugs in cancer medicine.

“These could include treatments that are currently deemed too expensive to fund on the NHS – however, in the future, treating only the patients that will benefit from certain treatments will save the NHS money in the long term.”

Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “New techniques such as these can enable drugs to be tailored to individual patients, and this could potentially improve cancer survival in the long term.

“Health professionals may in the future be able to use this information to direct treatment to patients most likely to benefit, and avoid giving treatment that is less likely to be effective to patients with drug resistant cancers.”

Source: BBC NEWS

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UK scientists say they have discovered why some women fail respond to breast cancer treatment, and it is a gene error they believe they can fix.

Tamoxifen is given to most women diagnosed with breast cancer to prevent the cancer returning.

But not all women respond to the drug – experts estimate a third get no benefit.

The work in the journal Cancer Research suggests the problem is too much of a gene called FGFR1.

This discovery could lead to new treatments for these women as scientists “switch off” the action of FGFR1, enabling Tamoxifen to work.

The team of scientists in the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research have already shown this is possible in the lab.

They introduced a drug which “switched off” the action of FGFR1.

Once FGFR1 was stopped, hormone-based treatments like Tamoxifen could get back to work in destroying cancer cells, they found.

The researchers believe this could ultimately help thousands of women each year.

They say one in 10 breast cancer patients has too much of the FGFR1 gene.

Dr Nick Turner, who led the research, said: “Understanding how this gene can cause Tamoxifen resistance reveals a new drug target for treating breast cancers in patients who would otherwise have a poor outcome.

“There are a number of drugs in development that stop FGFR1 working, and clinical studies are investigating whether these drugs work against cancers with too many copies of this gene.

“The next step is to set up a clinical trial to see whether a drug that blocks the action of this gene can counteract hormone therapy resistance in breast cancer patients.

“If these trials confirm our lab work we could be on the verge of a potentially exciting new treatment for breast cancer.”

Dr Lesley Walker of Cancer Research UK, the charity which helped fund the work, said: “Cracking the problem of resistance to treatments such as Tamoxifen would be a major advance in treating breast cancer.”

Breast cancer is the most common cancer in the UK affecting more than 45,500 women each year.

Tamoxifen blocks the female sex hormone oestrogen that fuels the growth of some breast tumours.

Source: BBC NEWS

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A gene known to shield the body from harmful chemicals may also protect against bowel cancer, a study suggests.

Dundee scientists found that removing a single gene from mice predisposed to cancers of the small intestine led to a 50-fold increase in tumours.

The rise in adenomas – pre-cancerous growths – appeared to be linked to increased inflammation of the bowel, the study in the journal PNAS reported.

The GSTP gene has previously been linked to a reduction in lung tumours.

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Several studies have shown it appears to provide protection to both the lungs and the skin against cancerous growths. But this latest research from the University of Dundee suggests in the bowel it may work in another way.

Specifically it found that there was more inflammation in the small intenstines of mice who had the GSTP gene removed.

Inflammation has already been associated with the risk of developing polyps – some types of which may go on to become cancerous, like adenomas – and it may be here that the gene plays a protective role.

Doctors already know of two genetic conditions which increase the risk of developing bowel cancer: FAP, or familial adenomatous polyposis, and HNPCC, which stands for hereditary non-polyposis colorectal cancer.

These conditions are however only responsible for about one in 20 cases of bowel cancer.

Inflammatory responses

The findings do not have any immediate clinical application, but experts note studies have suggested that certain types of food such as broccoli may boost GSTP levels.

“If this can be confirmed in humans, it could suggest another way of reducing the risk of bowel cancer,” said Dr Lesley Walker, director of cancer information at Cancer Research UK, which funded the research.

Dr Rob Glynne Jones, chief medical adviser at Bowel Cancer UK welcomed the latest research.

He said: “We are beginning to realise that inflammatory responses are very important – both in terms of a predisposition to cancer but also how you respond to treatment.

“We are in the process of unravelling the story, and a study like this is another piece of the jigsaw. Anything we can find out about possible causes helps us at every level – and what this looks like here is another potential pathway to disease.”

Professor William Steward of Beating Bowel Cancer said it was encouraging that this was a gene which could be influenced by diet.

“These findings lead to the possibility of developing approaches to preventing colorectal cancer,” he said. “Given the marked rise in the number of cases of bowel cancer, in particular among young people, this research could have important implications for reducing the risk and for tackling this worrying trend.”

Source: BBC NEWS

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Genetic warning signs of an increased risk of the commonest kind of brain cancer have been discovered.

UK and US scientists identified genetic indicators that someone is at greater risk of developing a glioma – which accounts for 50% of all brain tumours.

However, the teams from London, Texas and California write in Nature Genetics that environmental factors also affect if someone will develop the cancer.

A UK charity said the work opened up new avenues for research and treatment.

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About 4,550 people are diagnosed with brain tumours each year. Only 14% are alive after five years.

Gliomas begin in glial cells, which play a key role supporting and insulating nerve cells in the brain.

There are various kinds, with glioblastoma being the most aggressive, deadly and common.

People who are diagnosed with it rarely survive more than five years.

Analysis

The two research teams looked at single nucleotide polymorphisms (SNPs). These are points in the genetic code which vary from person to person.

In the first study, a team of scientists from London’s Institute of Cancer and the University of Texas looked at over 521,000 SNPs in almost 1,900 glioma patients and 3,670 healthy people and found 34 SNPs linked with glioma.

These 34 were then independently analysed by scientists in Germany, France and Sweden who looked at the DNA of 2,500 people with glioma and almost 3,000 healthy people.

This allowed researchers to pinpoint 14 key SNPs on five genes.

As people have two copies of each gene, one from each parent, they can have up to 10 of the variants.

The researchers said those who had eight or more were three times more likely to develop glioma than the general population.

Professor Richard Houlston of the Institute of Cancer Research, who led the study, said: “This is a major discovery.

“We’ve found the first real evidence that variations in the genes which many people carry can increase their risk of this deadly disease.”

The team hope their findings can eventually be used to help identify those most at risk for the disease and also to provide potential targets for treatment or prevention.

‘Relative risk’

In the second study, a team from the Mayo Clinic and the University of California San Francisco found a connection between DNA alterations on chromosome 9 and glioblastoma risk.

They looked at the DNA of over 900 glioma patients, and 4,000 healthy people.

It was found that people with three particular SNPs had a 50% increased risk of developing glioblastoma.

The same section of chromosome 9 was one of the five points identified by the Institute of Cancer Research study.

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But the Mayo Clinic’s Dr Robert Jenkins, who led the research, said having the SNPs did not mean someone was guaranteed to get the cancer.

“Increased relative risk is just that – relative.”

A normal person’s risk of developing a glioblastoma is about one in 10,000, but the researchers say the risk is about one in 7,000 for a person carrying one of these SNPs.

However, scientists in both studies say further research is needed to confirm their findings, and that it is too early to screen people for the genetic variations.

Professor Melissa Bondy, of the University of Texas, said: “We have only just begun to understand the causes of brain tumours.

“Our findings give reasons for hope for those who might be affected and an incentive for a more comprehensive investigation of what has been a mysterious disorder.”

And Dr Lesley Walker, director of information at Cancer Research UK, which part-funded the UK study, said: “Compared with many other cancers, little is known about the lifestyle or genetic factors that influence the risk of developing brain tumours.”

She said it was important to “unlock” some of the “genetic secrets” behind glioma.

“Identifying these genetic variants will open up new avenues for scientists to explore, helping them to better understand how gliomas develop, identify who might be most at risk and ultimately find improved ways to diagnose and treat the disease,” she added.

Source: BBC NEWS

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A type of drug designed to stunt tumour growth has actually been found to fuel cancer if given at too low a dose.

UK scientists were investigating a kind of drug called an anti-angiogenesis, still under development, which hampers the growth of tumour blood vessels.

Avastin and Sutent, which act in a similar way, have been proven to work and were not covered in this research.

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But cancer experts say the study in Nature Medicine could help make those drugs more effective.

The researchers focused on a drug called Cilengitide which is designed to prevent blood vessel cells sticking together and moving – an important part of angiogenesis.

Previous tests on people have found that a few patients with brain tumours benefited from high doses of the drug, but that it failed to work for most.

In this research, tests carried out on mice showed that low doses of Cilengitide actually stimulated the growth of cancers.

Further investigation showed it did this by switching on a molecule called VEGFR2, which triggers the angiogenesis process.

That is significant because although when a patient is initially given a drug, its level in the blood rises quickly ensuring a big dose goes to the tumour, after a while levels start to fall as the body begins to deal with the drug.

This is likely to be why trials of the drug have shown such poor results.

Caveat

Dr Kairbaan Hodivala-Dilke of the Institute of Cancer, who led the study, said it was important that the trials looking at this drug continued.

“We’ve got evidence now that low doses can enhance tumour growth. So there is no benefit of giving a high dose, which then drops, and then a high dose again.

“But that’s not to say it can’t work at all. It can, but there is this caveat.”

She said it may be more effective to give the drug via an infusion pump, which would allow the dosage to remain topped up at an effective level.

Dr Andy Reynolds, from the Breakthrough Breast Cancer Research Centre at the Institute of Cancer Research, who also worked on the study, said: “Knowledge of this mechanism will help us develop new ways to make these drugs as effective as possible.

“In the future, we may be able to combine these inhibitors with other drugs to maximise their effectiveness for patients.”

Dr Lesley Walker, director of cancer information at Cancer Research UK, which helped fund the research, said: “This study is important because it may help to explain the mixed results previously seen in patients and turn around disappointing results so people may still benefit from the drug without the potential harm.”

Mechanisms

The research also has implications for the existing drugs Sutent, used to treat kidney cancer, and Avastin, for colorectal cancer.

They work by the same process, but on different targets.

At the moment, they can extend a patient’s life by several months. Experts hope that this research could lead to a better understanding of the drugs’ mechanisms and so to ways of making them more effective.

Dr Walker said: “Sutent and Avastin have proven effective enough for use in the NHS but there is still need to understand why they can sometime fail.

“It may be that there are similar mechanisms at work.”

Last month, the National Institute for Health and Clinical Excellence – the NHS’s drugs appraisal body – said Sutent could be considered for people with advanced kidney cancer. However, it decided against recommending Avastin for advanced colorectal cancer.

Source: BBC NEWS

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A “danger receptor” that may kick-start an immune reaction to cancer in the body has been found by UK researchers.

It picks up signs of cell death caused by injury or tumours and mobilises the body’s defences, Nature reports.

The finding may explain why some tumour-killing drugs partly work by setting off an immune response.

Better understanding of the receptor could help develop cancer treatments that harness the immune system, the London Research Institute team said.

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Cell death is a normal process in the body which keeps growth and repair ticking over and keeps tissue healthy.

But sometimes there is an abnormal type of cell death called necrosis.

It has been thought for many years that the body somehow senses this abnormal cell death and sets off an immune reaction.

From an evolutionary point of view this would make sense as injury puts the body at risk of infection and an immune response would be a sensible precaution.

However, until now no receptor capable of detecting this abnormal cell death had been found.

The researchers discovered that the DNGR-1 receptor on a type of immune cell called a dendritic cell mobilises an immune response after coming across this abnormal cell death.

Dendritic cells act as messengers, alerting other types of immune cells to kill invaders, such as viruses and bacteria.

Trigger

The researchers said tumours could also trigger this type of immune reaction because they often contain clusters of cells undergoing this type of cell death as they have a limited blood supply.

Dr Caetano Reis e Sousa, lead author based at Cancer Research UK’s London Research Institute, said: “After a 15-year hunt, we’ve identified the first ‘danger receptor’ – one which senses abnormal cell death and then triggers an immune response.

“The detection of ‘danger’ could explain some situations when a tumour triggers an immune reaction against itself.”

He said manipulating this system could be beneficial in treating cancer but also in other areas, such as preventing rejection in organ transplantation.

“There is a theory that some cancer-killing drugs kill tumour cells in such a way that triggers the immune system against them so they have a double whammy.”

Dr Lesley Walker, director of information at Cancer Research UK, said: “The concept of using the body’s immune system to fight cancer has been around for decades, but advances in recent years have made this field of research a very exciting one.

“The results of this study are really important scientifically and a step towards understanding how to manipulate the immune system to treat cancer in the future.”

Source: BBC NEWS

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A study has suggested using aspirin could cut the risk of developing a type of stomach cancer by up to a third.

The British Journal of Cancer study looked at over 300,000 people.

It found those who had taken aspirin in the previous year were far less likely to develop cancer of the middle or lower stomach.

Taking aspirin regularly is known to cut the risk of bowel cancer, but can have side effects, including causing bleeds within the abdomen.

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Such side effects mean that doctors advise against regular aspirin use as a protection against cancer.

This study followed 311,115 people for around seven years and analysed their use of the painkillers in the 12 months prior to the study starting.

A total of 73% of the group had used aspirin and 56% had used other NSAIDs at least once in the 12 months prior to the start of the study.

A quarter reported daily aspirin use while 10% reported daily use of other NSAIDs.

The rate of non-cardia stomach cancer calculated in this study was seven per 100,000 person-years for aspirin users, compared with 11 per 100,000 person-years for non-users.

Each year in the UK, around 8,000 people are diagnosed with stomach cancer, and around 5,250 people die from the disease.

Survival rates

There was also a 32% reduction for the same type of stomach cancer, non-cardia gastric cancer, in people who used other types of non-steroidal anti-inflammatory drugs – or NSAIDs – such as ibuprofen.

In contrast to results of previous studies, the researchers found that aspirin does not protect against oesophageal cancer and cardia gastric cancer – cancer of the top of the stomach.

Scientists believe that placebo controlled trials, which would assess risks and benefits should be conducted to see if NSAIDs can be used to protect against stomach and oesophageal cancers.

Five year survival rates for stomach cancers is just 15%, and for oesophageal cancers it is 8%.

‘Talk to your doctor’

Dr Christian Abnet, of the National Cancer Institute in America who led the research, said: “We found that the risk of non-cardia stomach cancer was lower in people who had taken aspirin, and this risk lowered the more regularly they took it.

“Interestingly, our results didn’t show a significant cut in the risk of oesophageal or cardia stomach cancer, so it’s important that we continue to review data that suggests otherwise.”

He added: “The number of people who survive at least five years following a diagnosis of stomach or oesophageal cancer is low, so it’s important to increase our understanding of ways to prevent the disease and to investigate aspirin as a possible preventative drug.”

He suggested that a further research should be carried out to further investigate the apparent protective benefits of aspirin and other NSAIDs, and the risk of side-effects.

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “It’s far too early to recommend that people take aspirin to protect themselves from these cancers.

“In cancers where survival is low, understanding how to prevent the disease is crucial, but more research is needed to discover how side effects can be balanced with the benefits.

“Cancer Research UK would urge people to speak to their doctor before taking aspirin regularly.”

Source: BBC NEWS

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Scientists say they have discovered a missing link in the way cells protect themselves against cancer.

They have uncovered how cells switch a gene called p53, which can block the development of tumours, on and off.

The researchers say the finding has important implications for cancer treatment and diagnosis.

The study, published in Genes And Development, was carried out by teams of scientists in Singapore and the University of Dundee.

The p53 gene, first discovered 30 years ago, plays a vital role in keeping the body healthy by ordering damaged cells to commit suicide, or by stopping them dividing while key repair work is carried out.

In half of all cancers the gene is either damaged or inactive, giving damaged cells a free rein to keep dividing and form cancer.

In the latest study, the scientists used a genetic trick to make zebrafish turn green when the p53 gene was switched on to explore the way it was regulated.

They found that the p53 gene makes not only the well-established p53 protein, but also an alternative “control switch” variation of the p53 protein – known as an isoform.

Radiation doses

Normally zebrafish, which carry the same p53 gene as humans, can survive low doses of radiation, which causes damage to the DNA, because the gene steps in to repair that damage.

But no such repair took place in zebrafish without the isoform switch, and they died after radiation exposure.

The researchers said this proved that the switch played a crucial role in enabling p53 to do its repair work.

Lead researcher Professor Sir David Lane, said: “The function of p53 is critical to the way that many cancer treatments kill cells since radiotherapy and chemotherapy act in part by triggering cell suicide in response to DNA damage.

“So understanding more about how this gene is controlled in cells is really important in finding ways to prevent cells from turning cancerous.”

Lesley Walker, Cancer Research UK’s director of cancer information, said: “This is a really exciting study which improves our understanding of how the p53 gene works.

“Discovering how it is regulated will have incredibly important implications in the development of better drugs and ways to diagnose cancer.”

Source: BBC NEWS

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Cancer cells cheat death by reversing a process which causes normal cells to commit suicide at the end of their natural life, scientists have shown.

They showed cancer cells were able to recover even after exposure to a chemical cocktail which triggers suicide in normal cells.

The ability may help cancer cells to block the effect of chemotherapy drugs.

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The study, by the Chinese University of Hong Kong, appears in the British Journal of Cancer.

Programmed cell suicide – or apoptosis – plays a key role in keeping the body healthy, by ridding it of damaged or defective cells.

If these cells are not destroyed, then they can may continue to divide, developing into a tumour.

The researchers treated human cervical, skin, liver and breast cancer cells each with three different chemicals – jasplakinolide, staurosporine and ethanol – which triggers apoptosis in normal cells.

They wanted to see if cancer cells could survive once they have passed the point of no return for normal cell death.

The researchers found the cancer cells recovered once the chemical cocktail had been removed – even after the cells had passed normal critical checkpoints.

Changing shape

When the chemicals were removed, the cancer cells regained their shape, function and continued to divide.

They only lost the ability to recover once the nucleus at the very heart of the cell containing key genetic material had started to disintegrate – an event right at the end of the normal cell suicide process.

Researcher Professor Ming-Chiu Fung said the study suggested that cancer cells could use this ability to survive assault by chemotherapy drugs.

He said the discovery could potentially help the development of new, more effective anti-cancer drugs.

Dr Lesley Walker, of the charity Cancer Research UK, said: “This eye-opening discovery has created an entire map of new routes to explore in the search for new therapy targets.

“It is an intriguing advance and one that we hope will play a useful part in our efforts to beat cancer.”

Source: BBC NEWS

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A new imaging technique can locate previously undetectable early stage cervical cancers.

A pilot study suggests it will enable doctors to carry out precise surgery to remove the tumours, rather than having to opt for a full hysterectomy.

The Institute of Cancer Research team say this should mean more patients can retain their fertility.

Details of the technique – diffusion weighted imaging – feature in the journal Radiology.

Using a vaginal probe, it works by exploiting differences in the motion of water within cancerous and healthy tissues.

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This produces images with a higher level of contrast between developing tumours and the surrounding healthy tissue than have been possible using the traditional external pelvic scan.

The pilot study, based on 59 women with cervical cancer aged between 24 and 83, produced highly promising results.

The researchers found 88% of tumours could be detected using an internal probe and diffusion-weighted imaging, compared with only 77% using external scans.

Accuracy

Lead researcher Professor Nandita deSouza said the new technique could not only pinpoint the location of tumours, it could also accurately determine their size.

She said: “With conventional scanning techniques, small tumours are harder to identify or to differentiate from scar tissue, particularly if the patient has had a recent biopsy.

“In these cases, conventional imaging can overestimate the level of cancer within the cervix and result in major surgery leading to infertility.

“The quality of the information from the images produced using this new method has allowed us to identify and define smaller tumours more accurately.

“We can use this information to plan less radical surgery, preserving as much of the uterus and the cervix as possible.”

Dr Lesley Walker, director of cancer information at Cancer Research UK, which funded the study, said improvements to imaging research to boost detection and diagnosis of cancers was a priority for the charity.

She said: “This small study is extremely promising and provides a clear rationale for more extensive studies.”

Around 2,700 women are diagnosed each year in the UK, making it the second most common cancer in women under 35. Approximately 1,000 women a year die from the disease in the UK.

Source: BBC NEWS

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