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PostPosted: Sat Mar 27, 2010 8:44 am 
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New Cancer Biomarker May Herald Personalized Medicine

ScienceDaily (Mar. 26, 2010) — Scientists at Oxford University have led a study that shows how simple diagnostic tests to identify which patients will respond to which cancer drugs can be developed, potentially ushering in a new era of personalised cancer medicine.

The Oxford researchers, with colleagues at the MD Anderson Cancer Center at the University of Texas, Houston, confirm their approach works in results published in the journal PNAS. They show that a specific protein can be used as a 'biomarker' to identify which patients with a rare type of non-Hodgkin lymphoma would benefit from a new class of cancer drug. 'This is the first report of a biomarker that predicts how a patient's cancer will respond to a cancer drug,' says Professor Nick La Thangue of Oxford University, who led the research. 'The presence or absence of the biomarker can now be used as a diagnostic test to identify which patients will benefit from this drug.

'It's one of the first examples of being able to personalise cancer medicine and tailor treatment for the individual patient,' he adds.

Biomarkers also have implications for reducing the cost burden of introducing new cancer drugs on the NHS, as only the subset of patients that would see a benefit would receive the treatment.

'New cancer drugs would be more likely to gain approval from the National Institute for Health and Clinical Excellence where biomarkers exist to identify the appropriate patient group,' believes Professor La Thangue, as their analyses of how well the treatment works in relation to how much it costs the NHS would improve.

Cancer drug discovery and development has changed significantly with greater understanding of what goes wrong in biological processes within cancer cells. New drugs target a variety of these cellular processes, but they will often only be effective in a subset of patients according to the profile of their particular cancer.

For example, trastuzumab (Herceptin) is an effective drug against breast cancer but only among those patients with cancers that express the protein which the drug targets. Patients without that protein see no benefit from the drug.

A biomarker is something that can be measured to predict whether a particular cancer will respond to treatment with a particular drug. Simple diagnostic tests based on the level of biomarker present can then flag up patients that will respond to that drug.

Biomarkers can also be used to identify appropriate patient groups for clinical trials. This would improve the ability of the trial to determine a drug's clinical benefits and increase the likelihood that new and effective drugs make it into clinics. Currently the failure rate for new drugs in development is estimated to be 80%.

The Oxford and Texas team focussed on a new class of cancer drug called HDAC inhibitors because they stop the action of the protein histone deacetylase. SAHA (Vorinostat or Zolinza) was the first drug of this class to gain regulatory approval, and can be used in the treatment of a rare type of non-Hodgkin lymphoma known as cutaneous T-cell lymphoma, or CTCL.

The researchers used a whole-genome screen to identify those genes active in CTCL cells that govern whether the cancer cells respond to the drug SAHA or not. The screen works by silencing each gene in turn to assess its effect on how well the drug works. HR23B was found to determine the CTCL cells' sensitivity to SAHA.

The scientists now report that HR23B works as a biomarker in a clinically relevant setting. The presence of HR23B in biopsies from patients with CTCL predicted who would respond to the treatment 71.7% of the time.

With this first demonstration of a predictive biomarker for a cancer drug, the approach using a whole-genome screen can be done again and again to find biomarkers for different cancers and different drugs. The hope is that the identification of new biomarkers can become routine.

The Oxford group has a patent on the whole-genome screen for identifying biomarkers and is looking at options for commercialising a biomarker kit using HR23B as a companion diagnostic test to go with the drug SAHA.

'This new work validates our approach for identifying biomarkers,' says Professor La Thangue. 'It should be possible to find biomarkers for every drug on the market and every drug in development and truly personalise cancer medicine.

'You can imagine in the future a biopsy will be taken of a patient's tumour and screened for the presence of a hundred different biomarkers. They'll then be given a cocktail of drugs that is tailored for the profile of their particular cancer,' he adds.

http://www.sciencedaily.com/releases/20 ... 230239.htm


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PostPosted: Sat Mar 27, 2010 8:47 am 
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Personalized Medicine: Moving Forward Slowly But Surely

ScienceDaily (Feb. 12, 2008) — With its promises of more effective, low-cost therapies for cancer, heart disease, Alzheimer's and other medical conditions, personalized medicine is moving forward but at a slow pace that's not keeping up with its high expectations, according to the article "Personalized Medicine" scheduled for the Feb. 11 issue of Chemical & Engineering News.

In the magazine's cover story, C&EN Senior Editor Rick Mullin notes that personalized medicine, the practice of catering medical therapies to the specific genetic and disease profiles of patients, represents a major shift from the one-size-fits-all model of traditional medicine. Despite its promise, researchers have had difficulty translating new genetic knowledge into effective therapies.

But fueled by new research tools and new genetic information, the field is silently moving forward. Notable successes include the development of Herceptin, a targeted therapy for breast cancer, and Gleevec, a treatment for lung cancer.

Other targeted therapies are in the pipeline. "We are at a kind of crossroads where we have developed a large number of new agents with pharmacologically sound activities," C&EN quotes one researcher. "But clearly, to hit the home run, you have to match the right drug to the right patient. It's easier said than done."

http://www.sciencedaily.com/releases/20 ... 094056.htm


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PostPosted: Thu Apr 15, 2010 10:52 am 
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Personalized Medicine for Cancer Patients in a New Technology Era

ScienceDaily (Apr. 14, 2010) — Published online in Nature, a paper authored by over 200 members of the International Cancer Genome Consortium (ICGC) describes the beginnings of a Brave New World, a new era of personalised medicine for cancer patients.

Formed in 2008, the consortium brings together leading cancer researchers from around the world, working together to catalogue the genetic changes of the 50 most common cancers -- 500 genomes from each cancer type -- and make the results freely available on the internet.

"Given the tremendous potential for relatively low-cost genomic sequencing to reveal clinically useful information, we anticipate that in the not so distant future, partial or full cancer genomes will routinely be sequenced as part of the clinical evaluation of cancer patients," say the authors in the paper.

Their statement is fairly low-key, given the staggering scale of progress over the last couple of decades. The first human genome project, which sequenced half a dozen people, cost 1.5 billion dollars and took 15 years. The same amount of data can now be processed in a week at a fraction of the cost.

"This is already revolutionising the way we do cancer research," said Professor Andrew Biankin, member of the Nature paper's writing team, researcher at Sydney's Garvan Institute of Medical Research, surgeon at Sydney's Bankstown Hospital and co-leader of the Australian Pancreatic Cancer Genome Initiative, the Australian project arm of the ICGC.

"The challenge in the past was to generate information. The challenge now is to manage the volume being generated daily -- finding ways to interpret, test and apply it appropriately."

"The consortium is providing the global research community with the best possible research tool -- how to select the next clinical trial. Whole genome sequencing allows us to pinpoint the exact molecular aberrations of each tumour. Understanding the aberrations allows you to target them with drugs."

"For example, you might find that the aberrations in a subtype of colon cancer are the same as the aberrations in a subtype of melanoma. In that case, the treatment that works in the colon cancer may be appropriate for the melanoma. So you'd go ahead and test it."

"The problem we have is the complexity of cancer. No two tumours are the same, even within the same type of cancer. They may look the same under the microscope, but their molecular aberrations vary greatly."

"When we treat a cancer, we give a person the drug that's most likely to work -- within the limitations of our current understanding. The drug may not work for that individual, even though it works for the majority of patients with the same kind of cancer. If the treatment fails, we go onto the second-line treatment, which might also fail. By the time we get to the treatment that's actually going to work, it might be third or fourth down the line and the cancer may have advanced. In the case of pancreatic cancer, the patient has probably died."

"The consortium's internet-based databanks will help us treat specific cancers with specific treatments. Not only that, the information will help us understand why some treatments work and others do not, and then design better drugs to target faulty elements or mechanisms."

"One of the first things we can do is pick the low hanging fruit -- things not detected by the old technologies. For example, if an existing therapy targets molecular aberrations in one cancer type, yet its effects have not been explored in other cancer types, we now have a rapid way of identifying which of the unexplored cancers is a likely new target."

"B-RAFF inhibitors are a good example of a drug that shows promise for treating some kinds of melanoma. If you were to test the drug with 50 other cancers, it could take 50 years, using old methods and technologies."

"If you approach the problem with new technologies, you can quickly match the drug with molecular aberrations in specific cancers, and narrow the trial phase down to a few months."

Australia's and Canada's pancreatic project groups will be among the first to release initial data on the web, alongside the UK (breast cancer), China (gastric cancer) and Japan (liver cancer). The data release and web access is timed to coincide with the publication of the Nature paper.

There will be various tiers of access, with ethical guidelines and governance in place to regulate who can see what. The general public will be able to see general summaries, while members of the research community will be able to request detailed reports, depending on their needs.

Pancreatic cancer sequencing in Australia will be undertaken by Professor Sean Grimmond from the University of Queensland's Institute for Molecular Bioscience in Brisbane, co-leader of the Australian team with Professor Biankin. (See details of the Australian arm of the ICGC project below.)

"We've just done a handful of sequences -- and already we know for sure that real cancer looks substantially different from the cell lines we've been using in the lab," said Biankin.

"We've hypothesised about that in the past, but having the evidence to prove the difference is exciting. Right from the outset we know everything there is to know about one person's tumour at the genomic, transcriptomic and epigenomic levels. We might not understand it, but we've got the data."

While not described in the paper, Biankin's group is using mice to host slices of human pancreatic tumour, effectively running pseudo clinical trials in the animals.

"It's great that we have the sequencing information as it allows us to run these parallel human-type trials in mice, testing a range of drugs against the specific molecular targets we know to exist in the tumour. It saves decades doing real clinical trials in people."

"While researchers have applied xenografts to mice in the past, they have not had the resources or information to run tests as speedily or systematically as this."

Australia's Contribution to ICGC

Australia is making a substantial contribution to the International Cancer Genome Consortium by tackling pancreatic cancer, one of the deadliest cancers and fourth most common cause of cancer death.

The Australian team is being led by Professor Sean Grimmond from the University of Queensland's Institute for Molecular Bioscience in Brisbane and Professor Andrew Biankin from the Garvan Institute of Medical Research in Sydney. It also involves collaborative contributions from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Johns Hopkins University in Maryland, the Ontario Institute for Cancer Research and the University of California, San Francisco.

The project is being funded through the National Health and Medical Research Council of Australia (NH&MRC), and at $27.5 million it is the largest single grant the NH&MRC has ever awarded. Further support is being provided by The Cancer Council NSW, the Queensland Government, the Garvan Institute and the University of Queensland. Applied Biosystems Inc. and Silicon Graphics, large international companies specialising in gene expression array analysis and high performance computing systems respectively, are also making significant contributions.

http://www.sciencedaily.com/releases/20 ... 130828.htm


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PostPosted: Thu Apr 15, 2010 10:54 am 
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Personalized Medicine: Moving Forward Slowly But Surely

ScienceDaily (Feb. 12, 2008) — With its promises of more effective, low-cost therapies for cancer, heart disease, Alzheimer's and other medical conditions, personalized medicine is moving forward but at a slow pace that's not keeping up with its high expectations, according to the article "Personalized Medicine" scheduled for the Feb. 11 issue of Chemical & Engineering News.

In the magazine's cover story, C&EN Senior Editor Rick Mullin notes that personalized medicine, the practice of catering medical therapies to the specific genetic and disease profiles of patients, represents a major shift from the one-size-fits-all model of traditional medicine. Despite its promise, researchers have had difficulty translating new genetic knowledge into effective therapies.

But fueled by new research tools and new genetic information, the field is silently moving forward. Notable successes include the development of Herceptin, a targeted therapy for breast cancer, and Gleevec, a treatment for lung cancer.

Other targeted therapies are in the pipeline. "We are at a kind of crossroads where we have developed a large number of new agents with pharmacologically sound activities," C&EN quotes one researcher. "But clearly, to hit the home run, you have to match the right drug to the right patient. It's easier said than done."

http://www.sciencedaily.com/releases/20 ... 094056.htm


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PostPosted: Mon May 10, 2010 2:59 pm 
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Drug Now Used to Treat Erectile Dysfuncton May Enhance Delivery of Herceptin to Certain Brain Tumors

ScienceDaily (May 7, 2010) — New research by scientists at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute suggests that a drug currently approved to treat erectile dysfunction may significantly enhance the delivery of the anti-cancer drug Herceptin to certain hard-to-treat brain tumors. The research, published in the journal PLoS ONE, could help doctors improve treatments for lung and breast cancers that have metastasized to the brain.

While cancers that originate in the brain are relatively rare -- approximately 22,000 patients are diagnosed with a primary brain tumor every year -- nearly 10 times that many people develop brain tumors from cancers that began elsewhere in the body. Lung cancer remains the leading cause of cancer death in the U.S., and about 20 percent of lung cancers metastasize to the brain. Breast cancer and melanoma may also spread to the brain, and once this happens, the cancer becomes extremely difficult to treat and the prognosis turns poor.

Even if a cancer is susceptible to drugs, these drugs must penetrate the "blood-brain barrier" if they're to treat cancer that's metastasized to the brain. "Mother Nature created this barrier to protect our brains from dangerous substances, but here we need to get through the barrier to deliver the drugs, and that's a problem," says study author Julia Y. Ljubimova, M.D., Ph.D., a research scientist at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute in Los Angeles.

Keith Black, M.D., chairman of Cedars-Sinai's Department of Neurosurgery and director of the Maxine Dunitz Neurosurgical Institute, is the lead research scientist on this project and senior author of the paper. He has studied the blood-brain barrier for about two decades, and his work in this field received the Jacob Javits award from the National Advisory Neurological Disorders and Stroke Council of the National Institutes of Health in June 2000. Since then, research conducted by his team found that the erectile dysfunction drugs sildenafil (Viagra) and vardenafil (Levitra), which inhibit the enzyme phosphodiesterase 5 (PDE5), could increase the permeability of the blood-brain tumor barrier and boost the effectiveness of the chemotherapy drug doxorubicin.

"No matter how effective against cancer a chemotherapeutic agent may be, it can have little impact on brain tumors if it cannot cross the blood-brain tumor barrier," he said. "As we find new drugs that are able to target these tumor cells, it is imperative that we develop better ways to enable the medications to reach their targets."

In the current study, the researchers examined whether PDE5 inhibitors might also increase the blood-brain tumor barrier's permeability to Herceptin, a monoclonal antibody used to treat lung and breast tumors that are positive for HER2/neu. Herceptin is a large molecule that does not easily cross the blood-brain tumor barrier, a limitation that severely reduces its effectiveness at treating brain metastases.

The researchers first measured vardenafil's effects on the permeability of the blood-brain tumor barrier. Using a mouse model, the scientists showed that vardenafil led to a two-fold increase in the amount of Herceptin that reached brain metastases of lung and breast cancers. Next, they examined whether this increase in blood-brain barrier permeability improved Herceptin's effectiveness at treating these brain metastases by giving mice vardenafil in tandem with Herceptin. The results showed that the combination of vardenafil plus Herceptin boosted mean survival by 20 percent, compared to Herceptin alone (72+/-18 days versus 59+/-9 days).

Mice whose tumors were not HER2-positive did not experience the same increase in survival that those with HER2-positive tumors did when given vardenafil, indicating that the survival benefit was indeed due to an increase in the amount of Herceptin reaching the tumors, says Ljubimova.

"Now that we've demonstrated that big molecules can cross the blood-brain tumor barrier, we're going to continue this strategy with other big molecule drugs, such as nanomedicine drugs" says Ljubimova. "This opens a new world for brain tumor treatments."

http://www.sciencedaily.com/releases/20 ... 175257.htm


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PostPosted: Sun Sep 11, 2011 12:39 am 
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Awesome report about the New Cancer Biomarker May Herald Personalized Medicine.,
many others will get the useful information about such a useful topic,.


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PostPosted: Fri Sep 30, 2011 7:39 am 
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Breast cancer survivor's advice: think through options

During a routine gynecological exam when she was 38 years old, the doctor examining her breasts thought she felt something unusual.

"She didn't feel a lump," said Rowden, now 58 and living in Dallas. "She felt a thickening of the left breast. That was the first indication something might be wrong."

The doctor recommended that Rowden have a mammogram. She'd had a screening mammogram at age 35, so the technicians had a basis for comparison. "They could detect a change in the left breast," Rowden said. "From there, they recommended I have a biopsy."

Worry set in, she recalled.

"I had a friend who was diagnosed at age 36, so I was a little bit concerned," Rowden said. "But I wasn't freaked out. I just wanted to follow up and head off any problems."

This was before minimally invasive needle biopsies, so Rowden had a surgical biopsy, during which they found no cancer but did find areas of abnormal cell growth that put her at high risk for developing breast cancer.

Rowden said she was given two courses of action: They could monitor her closely, performing quarterly breast examinations, or she could have a bilateral mastectomy to remove her left breast.

"I ended up opting for the surgery, based on a feeling that I needed to take care of it," she said. Her mother had died of uterine cancer four years earlier, and Rowden said she's certain that weighed in her decision.

Her instincts were more correct than she could have known. During the surgery, doctors found a tumor in her left breast, in an area that was not part of the biopsy.

"I was actually quite relieved," Rowden recalled of hearing the news that she did, in fact, have breast cancer. "I had basically felt like, well, at least I didn't have this surgery for nothing."

After the tumor was tested, Rowden said, an oncologist told her that she could have chemotherapy but it might not be of much use. "He said it wouldn't buy me much benefit because I had a particularly slow-growing tumor," she said. "He presented it as my choice. I decided not to have chemotherapy."

She has remained cancer-free. However, she explained, breast cancer altered the course of her life.

She had been a technical writer, working on software manuals that few people ever read. After her surgery, she became a breast cancer advocate and now works as the vice president of survivorship and outcomes for Susan G. Komen for the Cure, a nonprofit group focused on combating breast cancer .

Among the most important advice she gives to women diagnosed with the disease, she said, is to slow down and take your time.

"It's not an emergency in terms of making a decision today," she said. "I think it's helpful to give people permission to do a little homework and think about the decisions they have to make."

http://yourlife.usatoday.com/health/med ... 50602716/1


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