Date: Thursday Mar. 8, 2012 7:17 AM ET

BOSTON Scientists are reporting what could be very bad news for efforts to customize cancer treatment based on each person's genes.

They have discovered big differences from place to place in the same tumour as to which genes are active or mutated. They also found differences in the genetics of the main tumour and places where the cancer has spread.

This means that the single biopsies that doctors rely on to choose drugs are probably not giving a true view of the cancer's biology. It also means that treating cancer won't be as simple as many had hoped.

By analyzing tumours in unprecedented detail, "we're finding that the deeper you go, the more you find," said one study leader, Dr. Charles Swanton of the Cancer Research UK London Research Institute in England. "It's like going from a black-and-white television with four pixels to a colour television with thousands of pixels."

Yet the result is a fuzzier picture of how to treat the disease.

The study is reported in Thursday's New England Journal of Medicine.

It is a reality check for "overoptimism" in the field devoted to conquering cancer with new gene-targeting drugs, Dr. Dan Longo, a deputy editor at the journal, wrote in an editorial.

About 15 of these medicines are on the market now and hundreds more are in testing, but they have had only limited success. And the new study may help explain why.

The scientists used gene sequencing to a degree that has not been done before to study primary tumours and places where they spread in four patients with advanced kidney cancer. They found that two-thirds of gene mutations they detected were not present in all areas of the same tumour. They also were stunned to see different mutations in the same gene from one part of a tumour to another.

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Setback in search for gene-based cancer treatment

Two key patent cases that no doubt will impact the future of personalized medicine are pending review by the US Supreme Court. What will the Court decide?

By Courtenay C. Brinckerhoff | March 7, 2012

The debate over the patenting of technologies related to diagnostic and personalized medicine continues to swell with no resolution in sight. The Supreme Court heard oral arguments in Mayo Collaborative Services v. Prometheus Laboratories, Inc. last December, but has not yet issued a decision. Just last month, the US Patent and Trademark Office held public hearings to gather information for the study on genetic testing that it will use to prepare a report for Congress on this issue. And, the Supreme Court is deciding whether to review the Federal Circuit decision in Association for Molecular Pathology v. Myriad Genetics, Inc. (the BRCAI/gene patenting case), although current speculation is that the Court may defer any action on this case until it issues its decision in Prometheus. While each of these proceedings raises different legal issues, they all relate to the ability to obtain or enforce patent rights on genes, tests, and methods used in personalized medicine.

Personalized medicine is the new frontier of healthcare. It offers the promise of treatments that are tailored to a patients individual situation, including the patients genetic makeup, the specific variation of the disease the patient suffers from, and the patients specific response to a given course of treatment. With personalized medicine, a patient can be given the most effective treatment, improving prognosis and saving considerable time and money on ineffective treatments. As noted on the US Food and Drug Administrations Pharmacogentics webpage, [p]harmacogenomics can play an important role in identifying responders and non-responders to medications, avoiding adverse events, and optimizing drug dose.

The question being debated is whether these advances are most likely to flourish within the patent system or outside of it. Do patents promote investment in personalized medicine or stifle innovation by suppressing competition? Do patients benefit from patented therapies, or do they suffer without treatments because they are too expensive? The Founding Fathers established the patent system in the US Constitution as an incentive to promote the Progress of Science and useful Arts, but should a different paradigm apply to medical inventions?

Companies working in this field cite the high cost of developing and validating personalized medicine therapies, and emphasize the need to obtain a return on their successful investments. Without the promise of some period of market exclusivity during which they can profit from their years of research, companies will not have any incentive to work in this fieldor any resources to do so.

On the other side of the debate, some doctors organizations and patient groups believe that the patent system is bad for the healthcare system. They say that it drives up costs and may prevent patients from obtaining a second opinion, because the patent owner can prevent others from administering patented tests. Many believe that research would continueat universities and institutions like the National Institutes of Healthand that more people would benefit because the advances would be available on a more widespread basis.

At its heart, this debate may be more of a public policy question than a legal one. People deciding this issue must keep in mind that most university research is funded by government grants and that NIH is a federal agency. We may want taxpayer money to support this kind of research, but it raises the same specter of big government and taxpayer burden as health care reform. Is a country that may not be ready to provide universal access to proven therapies willing to invest substantial amounts in research programs that may take years to yield any benefits?

Turning back to the law, the US Court of Appeals for the Federal Circuit has refused to draw a line that categorically prohibits patents on personalized medicine. In Prometheus, the court found that methods of optimizing the dose of a specific type of drug was patent-eligible subject matter, not an improper attempt to patent a natural phenomenon. In Myriad, the court found that isolated DNA associated with an aggressive form of breast cancer could also be patented without violating the prohibition against patents on products of nature because DNA does not naturally occur in an isolated form. Although the Supreme Court could reach a different conclusion in either or both cases, its refusal to categorically prohibit business method patents suggests that it may also approach this issue in a similar fashioncautiously and on a case-by-case basis. That would leave it to Congress to decide if a different approach is needed (such as compulsory licensing as discussed at the Patent Office hearing), or if the current incentives and rewards are striking an adequate balance between private investment and public benefit.

Courtenay C. Brinckerhoff is a partner at Foley & Lardner LLP, vice chair of the firms Chemical, Biotechnology & Pharmaceutical Practice, and editor of Foleys PharmaPatentsBlog.com. The opinions expressed here do not represent those of Foley & Lardner LLP or its clients.

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Opinion: On the Gene Patent Debate

WEDNESDAY, March 7 (HealthDay News) -- The genetic makeup of cancer cells differs significantly from region to region within a single tumor, according to new research that raises questions about the true potential of personalized cancer medicine.

With this treatment approach, doctors study a tumor's genetic makeup to determine which drugs would work best in a particular patient. But if the genetic mutations driving the cancer cells vary widely, a single tissue sample won't necessarily give the full picture.

This "targeted therapy" involves "sticking a needle into the primary tumor site and taking a small sliver of a tumor, doing a gene analysis, and creating a genetic profile of the tumor to predict how the tumor will behave," explained Dr. Dan Longo, an oncologist and deputy editor at the New England Journal of Medicine.

"What this paper tells us is that is an oversimplification of the complexity of tumors and their heterogeneity," he said. "If you look at different sites of the very same tumor and the very same person, one site might tell you a gene profile associated with a good prognosis and the other site will tell you a gene profile associated with a bad prognosis."

Longo wrote an editorial accompanying the new study, published in the March 8 issue of the New England Journal of Medicine.

In the study, scientists from Cancer Research UK London Research Institute took 13 biopsies, or tissue samples, from a patient whose kidney cancer had spread. The biopsies were from eight regions of the kidney tumor and four tumors in the chest and lungs.

Researchers also took normal tissue, sequenced the patient's genome and compared that to what they found in the biopsies.

Genetic analysis turned up 128 mutations in the tumors. But only about one-third, or about 40 of those mutations, were present in all of the biopsies.

"The majority of mutations are not shared in every biopsy," said senior study author Charles Swanton, a professor of cancer medicine at the research institute.

Swanton and his colleagues also analyzed tumor tissue samples from another three patients with kidney cancer. From a total of 30 biopsies from all four patients, 26 tissue samples had mutations that were highly heterogenous, or varied, from one another.

See more here:
Is Cancer Outwitting 'Personalized Medicine'?

BOSTON Scientists are reporting what could be very bad news for efforts to customize cancer treatment based on each persons genes.

They have discovered big differences from place to place in the same tumor as to which genes are active or mutated. They also found differences in the genetics of the main tumor and places where the cancer has spread.

This means that the single biopsies on which doctors rely to choose drugs are probably not giving a true view of the cancers biology. It also means that treating cancer wont be as simple as many had hoped.

By analyzing tumors in unprecedented detail, Were finding that the deeper you go, the more you find, said one study leader, Dr. Charles Swanton of the London Research Institutes Cancer Research UK. Its like going from a black-and-white television with four pixels to a color television with thousands of pixels.

Yet the result is a fuzzier picture of how to treat the disease.

The study is reported in Thursdays New England Journal of Medicine.

It is a reality check for overoptimism in the field devoted to conquering cancer with new gene-targeting drugs, Dr. Dan L. Longo, a deputy editor at the journal, wrote in an editorial.

About 15 of these medicines are on the market now and hundreds more are in testing, but they have had only limited success. And the new study may help explain why.

The scientists used gene sequencing to a degree that has not been done before to study primary tumors and places where they spread in four patients with advanced kidney cancer. They found that two-thirds of gene mutations they detected were not present in all areas of the same tumor. They also were stunned to see different mutations in the same gene from one part of a tumor to another.

That means a single biopsy would reveal only a minority of mutations. Still, its not clear whether doing more biopsies would improve accuracy, or how many or how often they should be done.

See the original post here:
Gene-based cancer research suffers setback, scientists say

BOSTON - Scientists are reporting what could be very bad news for efforts to customize cancer treatment based on each person's genes.

They have discovered big differences from place to place in the same tumour as to which genes are active or mutated. They also found differences in the genetics of the main tumour and places where the cancer has spread.

This means that the single biopsies that doctors rely on to choose drugs are probably not giving a true view of the cancer's biology. It also means that treating cancer won't be as simple as many had hoped.

By analyzing tumours in unprecedented detail, "we're finding that the deeper you go, the more you find," said one study leader, Dr. Charles Swanton of the Cancer Research UK London Research Institute in England. "It's like going from a black-and-white television with four pixels to a colour television with thousands of pixels."

Yet the result is a fuzzier picture of how to treat the disease.

The study is reported in Thursday's New England Journal of Medicine.

It is a reality check for "overoptimism" in the field devoted to conquering cancer with new gene-targeting drugs, Dr. Dan Longo, a deputy editor at the journal, wrote in an editorial.

About 15 of these medicines are on the market now and hundreds more are in testing, but they have had only limited success. And the new study may help explain why.

The scientists used gene sequencing to a degree that has not been done before to study primary tumours and places where they spread in four patients with advanced kidney cancer. They found that two-thirds of gene mutations they detected were not present in all areas of the same tumour. They also were stunned to see different mutations in the same gene from one part of a tumour to another.

That means a single biopsy would reveal only a minority of mutations. Still, it's not clear whether doing more biopsies would improve accuracy, or how many or how often they should be done.

Go here to read the rest:
Gene study suggests treating cancer is more complex than many had hoped

LONDON (Reuters) - Taking a sample or biopsy from just one part of a tumour might not give a full picture of its genetic diversity and may explain why doctors, despite using genetically targeted drugs, are often unable to save patients whose cancer has spread, scientists said.

A study by British researchers found there are more genetic differences than similarities between biopsies taken from separate areas of the same tumour, and yet further gene differences in samples taken from secondary tumours.

That might help explain why, despite recent development of a wave of highly targeted drugs designed to tackle cancers of specific genetic types, the prognosis remains poor for many patients with so-called solid-tumour disease like breast, lung, or kidney cancer that has spread to others parts of the body.

But the researchers, whose study was partly funded by charity Cancer Research UK and published in the New England Journal of Medicine, said it also pointed to a way forward.

The team carried out the first ever genome-wide analysis of the genetic changes or faults in different regions of the same tumour.

They looked at four patients with cancer in their kidneys, taking samples from different regions of the primary tumour and also from other organs where the tumour had spread.

They found that the majority of gene faults, around two-thirds, were not the same in one sample as in another, even when the biopsies were taken from the same tumour.

Samples taken from secondary tumours - which are a result of the disease spreading to other parts of the body - had yet more different genetic faults, suggesting that basing treatment decisions on just one primary tumour sample is not sufficient.

"We've known for some time that tumours are a patchwork of faults, but this is the first time we've been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumour in such exquisite detail," said Charles Swanton, of University College London's cancer institute, who led the study and presented its results at a briefing in London on Tuesday.

He said they had uncovered "an extraordinary amount of diversity" at a genetic level both within tumours and within a single patient, with more differences between biopsies from the same tumour than similarities.

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Cancer gene mutation more complex than previously thought -study

MOUNTAIN VIEW, Calif. -- In Silicon Valley, the line between computing and biology has begun to blur in a way that could have enormous consequences for human longevity.

Bill Banyai, an optical physicist at Complete Genomics, has helped make that happen. When he began developing a gene sequencing machine, he relied heavily on his background at two computer networking start-up companies. His digital expertise was essential in designing a factory that automated and greatly lowered the cost of mapping the three billion base pairs that form the human genome.

The promise is that low-cost gene sequencing will lead to a new era of personalized medicine, yielding new approaches for treating cancers and other serious diseases. The arrival of such cures has been glacial, however, although the human genome was originally sequenced more than a decade ago.

Now that is changing, in large part because of the same semiconductor industry manufacturing trends that opened up consumer devices like the PC and the smartphone: exponential increases in processing power and transistor density are accompanied by costs that fall at an accelerating rate.

As a result, both new understanding and new medicines will arrive at a quickening pace, according to the biologists and computer scientists.

"For all of human history, humans have not had the readout of the software that makes them alive," said Larry Smarr, director of the California Institute of Telecommunications and Information Technology, a research center that is jointly operated by the University of California, San Diego, and the University of California, Irvine, who is a member of the Complete Genomics scientific advisory board. "Once you make the transition from a data poor to data rich environment, everything changes."

Complete Genomics, based in Mountain View, is one of more than three dozen firms hastening to push the cost of sequencing an entire human genome below $1,000. The challenge is part biology, part chemistry, part computing, and in Complete Genomics' case, part computer networking.

Complete Genomics is a classic Silicon Valley start-up story. Even the gene sequencing machines, which are housed in a 4,000-square-foot room bathed in an eerie blue light, appear more like a traditional data center than a biology lab.

In 2005 ,when Clifford Reid, a successful Silicon Valley software entrepreneur, began to assemble his team, he approached Dr. Banyai and asked if he was interested in joining a gene sequencing start-up. Dr. Reid, who was also trained in physics and math, had spent a year as an entrepreneur-in-residence at the Massachusetts Institute of Technology, where he had become a convert to bioinformatics, the application of computer science and information technologies to biology and medicine.

Dr. Banyai had even less experience in biology.

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Cost of Gene Sequencing Falls, Raising Hopes for Medical Advances

Taking a sample or biopsy from just one part of a tumor might not give a full picture of its genetic diversity and may explain why doctors, despite using genetically targeted drugs, are often unable to save patients whose cancer has spread, scientists said.

A study by British researchers found there are more genetic differences than similarities between biopsies taken from separate areas of the same tumor, and yet further gene differences in samples taken from secondary tumors.

That might help explain why, despite recent development of a wave of highly targeted drugs designed to tackle cancers of specific genetic types, the prognosis remains poor for many patients with so-called solid-tumor disease like breast, lung, or kidney cancer that has spread to others parts of the body.

But the researchers, whose study was partly funded by charity Cancer Research UK and published in the New England Journal of Medicine, said it also pointed to a way forward.

The team carried out the first ever genome-wide analysis of the genetic changes or faults in different regions of the same tumor.

They looked at four patients with cancer in their kidneys, taking samples from different regions of the primary tumor and also from other organs where the tumor had spread.

They found that the majority of gene faults, around two-thirds, were not the same in one sample as in another, even when the biopsies were taken from the same tumor.

Samples taken from secondary tumors - which are a result of the disease spreading to other parts of the body - had yet more different genetic faults, suggesting that basing treatment decisions on just one primary tumor sample is not sufficient.

"We've known for some time that tumors are a patchwork of faults, but this is the first time we've been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumor in such exquisite detail," said Charles Swanton, of University College London's cancer institute, who led the study and presented its results at a briefing in London on Tuesday.

He said they had uncovered "an extraordinary amount of diversity" at a genetic level both within tumors and within a single patient, with more differences between biopsies from the same tumor than similarities.

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Cancer gene mutation more complex than previously thought