Archive for the ‘Personalized’ Category

Targeted Cancer Therapies Doomed to Fail?

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Posted 15 Jun 2012 — by James Street
Category Targeted Cancer Therapy

 

By Michael Smith, North American Correspondent, MedPage Today

Published: June 13, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

 

 

Resistance to targeted cancer therapies may be almost inevitable, at least if they are used alone, two groups of researchers reported online in Nature.

Mathematical modeling, based on genetic testing of colorectal cancer patients, suggests that resistance already exists even before targeted therapy begins, according to Luis Diaz, MD, of Johns Hopkins Kimmel Cancer Center, and colleagues.

One effect of single-agent targeted therapy, they noted, is to allow tumor cells containing resistance mutations to grow and prosper, leading to disease progression.

A second group, led by Alberto Bardelli, PhD, of the Institute for Cancer Research and Treatment in Turin, Italy, found some evidence of preexisting resistance, but added that resistance could also emerge as a result of single-agent targeted treatment.

The solution, both groups argued, may be to use combination therapies to delay or prevent progression.

Molecules that block the epidermal growth factor receptor (EGFR) often have a dramatic initial effect on cancers driven by the receptor, Diaz and colleagues noted.

But resistance almost always arises within a few months of starting therapy, leading to relapse, although the exact mechanisms of the resistance have been unclear.

To help clarify the situation, they studied 28 patients with metastatic colorectal cancer, a disease in which patients whose tumors have a wild-type KRAS gene are often sensitive to EGFR blockade.

Four of the patients already had KRAS mutations at the start of monotherapy with panitumumab (Vectibix), a monoclonal antibody aimed at EGFR. But nine of the remaining 24 with normal KRAS developed mutations about 5 or 6 months after starting treatment.

Mathematical modeling, Diaz and colleagues wrote, showed that the parent cells of those with KRAS mutations must have been present before the panitumumab treatment started.

“These resistance mutations develop by chance as cancer cells divide so that tumors always contain thousands of resistance cells,” Diaz said in a statement, adding that the findings likely apply to any targeted cancer therapy.

Co-author Bert Vogelstein, MD, also of Johns Hopkins, added that the finding means that “long-term remissions of advanced cancers will be nearly impossible with single targeted agents.”

The research team also noted that their method – testing tumor DNA found in the blood – is noninvasive and was able to detect changes in KRAS long before those changes translated into renewed tumor growth.

That should allow physicians the opportunity to alter the treatment, perhaps by adding agents to the regimen.

“The good news is that there is a limited number of pathways that go awry in cancer, so it should be possible to develop a small number of agents that can be used in a large number of patients,” Vogelstein said in a statement.

Bardelli and colleagues reached similar conclusions after studying colorectal tumor cell lines and a group of 10 patients with metastatic disease who were being treated with cetuximab (Erbitux), a chimeric antibody aimed at EGFR.

They found that preexisting KRAS mutations were amplified in one patient and emerged after treatment in six others.

The resistance mutations were detectable in blood samples as early as 10 months before radiological assessment confirmed that the disease had progressed, Bardelli and colleagues said.

“Our results suggest that blood-based noninvasive monitoring of patients undergoing treatment with anti-EGFR therapies … could allow for the early initiation of combination therapies that may delay or prevent disease progression,” they concluded.

The study by Diaz and colleagues was supported by The Virginia and D. K. Ludwig Fund for Cancer Research, the National Colorectal Cancer Research Alliance, the NIH, the National Cancer Institute, the European Research Council, the Austrian Science Fund, and the John Templeton Foundation.

The authors declared competing financial interests, including affiliations with Personal Genome Diagnostics and Inostics.

The study by Bardelli and colleagues had support from the European Union Seventh Framework Programme, the Associazione Italiana per la Ricerca sul Cancro, the Regione Piemonte, the Fondazione Piemontese per la Ricerca sul Cancro, Oncologia Ca’ Granda ONLUS, Mr William H. Goodwin and Mrs Alice Goodwin and the Commonwealth Foundation for Cancer Research, the Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center, the Society of MSKCC, the NIH, the Beene Foundation, and the Regione Lombardia and Ministerio Salute.

The authors declared they had no competing financial interests

Company Profile for Precision Therapeutics, Inc.

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Posted 19 May 2012 — by James Street
Category Personalized, Precision Therapeutics

press release

May 18, 2012, 10:40 a.m. EDT

May 18, 2012 (BUSINESS WIRE) — Precision Therapeutics, a leading life-science company based in Pittsburgh, Pennsylvania, is dedicated to personalized cancer care. Precision offers a portfolio of products developed to help guide physicians and patients with difficult clinical decisions throughout the cancer care continuum.

Precision’s state of the art Comprehensive Tumor Profiling is an integrated straightforward approach combining three core platforms of personalized medicine to capture the total sum of genomic, proteomic and functional information for each patient’s cancer through a portfolio of multi-platform tests for cancer treatment in multiple tumor types.

Precision’s first commercial test, ChemoFx(R), is a proprietary drug response marker which measures an individual’s malignant tumor response to a range of standard therapeutic alternatives under consideration by a physician. Precision currently receives ChemoFx(R) specimens from 271 top medical institutions including 20 of the 21 National Comprehensive Cancer Network (NCCN) Member Institutions, and 8 of the US News and World Report Top 10 Hospitals for Cancer Care. To date, over 77,000 patient specimens have been submitted for ChemoFx(R) testing using 105 unique chemotherapy treatments and combinations.

For more information, visit www.precisiontherapeutics.com or www.chemofx.com .

        
        Company:                Precision Therapeutics, Inc.
        Headquarters Address:   2516 Jane Street
                                Pittsburgh, PA 15203
        Main Telephone:         412-432-1500

www.precisiontherapeutics.com            Type of Organization:   Private
        Industry:               Biotechnology
        Key Executives:         CEO: Sean McDonald
                                VP Marketing: Roberta Coffin
        Public Relations
                                Pam Ranallo
           Contact:
                                412-432-1502
           Phone:
                                pranallo@ptilabs.com
           Email:

SOURCE: Precision Therapeutics, Inc.

DNA Sequencing Lays Foundation for Personalized Cancer Treatment

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Posted 03 Apr 2012 — by James Street
Category Bioinformatics, Gene sequencing, genetic research, Personalized, Washington University Cancer Genome Initiative

ScienceDaily (Apr. 1, 2012) — Scientists at Washington University School of Medicine in St. Louis are using powerful DNA sequencing technology not only to identify mutations at the root of a patient’s tumor — considered key to personalizing cancer treatment — but to map the genetic evolution of disease and monitor response to treatment.

“We’re finding clinically relevant information in the tumor samples we’re sequencing for discovery-oriented research studies,” says Elaine Mardis, PhD, co-director of The Genome Institute at the School of Medicine. “Genome analysis can play a role at multiple time points during a patient’s treatment, to identify ‘driver’ mutations in the tumor genome and to determine whether cells carrying those mutations have been eliminated by treatment.”

This work is helping to guide the design of future cancer clinical trials in which treatment decisions are based on results of sequencing, says Mardis, who is speaking April 1 at the opening plenary session of the American Association for Cancer Research annual meeting in Chicago. She also is affiliated with the Siteman Cancer Center at the School of Medicine and Barnes-Jewish Hospital.

To date, Mardis and her colleagues have sequenced all the DNA — the genome — of tumor cells from more than 700 cancer patients. By comparing the genetic sequences in the tumor cells to healthy cells from the same patient, they can identify mutations underlying each patient’s cancer.

Already, information gleaned through whole-genome sequencing is pushing researchers to reclassify tumors based on their genetic makeup rather than their location in the body. In patients with breast cancer, for example, Mardis and her colleagues have found numerous driver mutations in genes that have not previously been associated with breast tumors.

A number of these genes have been identified in prostate, colorectal, lung or skin cancer, as well as leukemia and other cancers. Drugs that target mutations in these genes, including imatinib, ruxolitinib and sunitinib, while not approved for breast cancer, are already on the market for other cancers.

“We are finding genetic mutations in multiple tumor types that could potentially be targeted with drugs that are already available,” Mardis says.

She predicts, however, that it may require a paradigm change for oncologists to evaluate the potential benefits of individualized cancer therapy. While clinical trials typically involve randomly assigning patients to a particular treatment regimen, a personalized medicine approach calls for choosing drugs based on the underlying mutations in each patient’s tumor.

“Having all treatment options available for every patient doesn’t fit neatly into the confines of a carefully designed clinical trial,” Mardis acknowledges. “We’re going to need more flexibility.”

When during the course of cancer mutations develop also is likely to be important in decisions about treatment. In a recent study, Mardis and her team mapped the genetic evolution of leukemia and found clues to suggest that targeted cancer drugs should be aimed at mutations that develop early in the course of the disease.

Using “deep digital sequencing,” a technique developed at The Genome Institute, they sequenced individual mutations in patients’ tumor samples more than 1,000 times each. This provides a read-out of the frequency of each mutation in a patient’s tumor genome and allowed the researchers to map the genetic evolution of cancer cells as the disease progressed.

They found that as cancer evolves, tumors acquire new mutations but always retain the original cluster of mutations that made the cells cancerous in the first place. Their discovery suggests that drugs targeted to cancer may be more effective if they are directed toward genetic changes that occur early in the course of cancer. Drugs that target mutations found exclusively in later-evolving cancer cells likely may not have much effect on the disease because they would not kill all the tumor cells.

Mardis says that sequencing the entire genome of cancer cells is essential to piecing together an accurate picture of the way cancer cells evolve. If the researchers had sequenced only the small portion of the genome that involves genes, they would not have had the statistical power to track the frequency of mutations over time. (Only 1 to 2 percent of the genome consists of genes.)

In another study, a phase III clinical trial of post-menopausal women with estrogen-receptor positive breast cancer, the Washington University researchers have shown that sequencing can help to predict which women will respond to treatment with aromatase inhibitors. These estrogen-lowering drugs are often prescribed to shrink breast tumors before surgery. But only about half of women with estrogen-receptor positive breast cancer respond to these drugs, and doctors have not been able to predict which patients will benefit.

Interestingly, by sequencing patients’ breast tumors before and after aromatase inhibitor therapy, the researchers identified substantive genomic changes that had occurred in responsive patients, whereas the genomes of unresponsive patients remained largely unchanged by the therapy.

“No one has ever looked at treatment response at this level of resolution,” Mardis says. “It’s so obvious who is responding.”

In addition, the researchers have identified a series of mutations in the breast tumors that have corresponding small-molecule inhibitor drugs that target defective proteins. This finding indicates that for women who are not responding to aromatase inhibitors, treatment options may include combining conventional chemotherapy with the indicated small-molecule inhibitor.

“We felt it was important to show there could be therapeutic options available to patients who are resistant to aromatase inhibitors,” Mardis says. “As we move forward, we think sequencing will contribute crucial information to determining the best treatment options for patients.”

The research is funded by the National Cancer Institute, the National Human Genome Research Institute and the National Heart, Lung and Blood Institute, all of the National Institutes of Health, and the Washington University Cancer Genome Initiative.

Deception at Duke: Fraud in cancer care?

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Posted 22 Feb 2012 — by James Street
Category Ethics, Ethics of Science, Fraud, Personalized
February 12, 2012 7:03 PM

Chemotherapy can be a tough road for people with cancer, often debilitating and even dangerous. Which is why five years ago, when Duke University announced that it had an advanced, experimental treatment that would match chemotherapy to a patient’s own genetic makeup, it was hailed as the holy grail of cancer care. The scientist behind the discovery was Dr. Anil Potti, and soon Dr. Potti became the face of the future of cancer treatment at Duke, offering patients a better chance even with advanced disease. However, when other scientists set out to verify the results, they found many problems and errors. What our 60 Minutes investigation reveals is that Duke’s so-called breakthrough treatment wasn’t just a failure — it may end up being one of the biggest medical research frauds ever.

The following is a script of “Deception at Duke” which aired on Feb. 12, 2012. Scott Pelley is the correspondent. Kyra Darnton, producer.

Five years ago, Duke University announced it had found the holy grail of cancer research. They’d discovered how to match a patient’s tumor to the best chemotherapy drug. It was a breakthrough because every person’s DNA is unique, so every tumor is different. A drug that kills a tumor in one person, for example, might not work in another. The research was published in the most prestigious medical journals. And more than a hundred desperately ill people invested their last hopes in Duke’s innovation.

In 2010, we learned that the new method was a failure. But what isn’t widely known, until tonight, is that the discovery wasn’t just a failure, it may end up being one of the biggest medical research frauds ever – one that deceived dying patients, the best medical journals and a great university.

[Dr. Anil Potti: Duke has made a commitment to fight this war against cancer at a much higher level.]

Dr. Anil Potti, featured in this commercial for Duke University, had made a discovery that promised to change the face of medicine.

[Potti: Genomics will revolutionize cancer therapy. It actually identifies a fingerprint that's unique to every individual patient.]

Dr. Rob Califf: This is sort of like the holy grail of cancer.

Dr. Rob Califf is Duke’s vice chancellor of clinical research.

Scott Pelley: Was the idea here that this would change the way we thought about treating cancer?

Califf: Well, you’ve never seen such excitement at an institution, and it’s understandable.

It wasn’t just Duke that was excited. A hundred and twelve patients signed up for the revolutionary therapy. Hope was fading for Juliet Jacobs when she learned about it. She had Stage IV lung cancer. And this would be her last chance.

Walter Jacobs: She was my best friend, but that’s kind of cliche. She’s, she’s somebody who after 49 and a half years, I was still madly in love with.

She and her husband Walter were looking into experimental treatments. They had to choose carefully because there was only time for one.

Scott Pelley: When you met Dr. Potti, what did you think?

Jacobs: We felt that he was going to give us a chance. He was… He was very encouraging.

For a patient with no time, Dr. Potti’s research promised the right drug, right now.

Pelley: Fair to say Potti was a rising star at Duke?

Califf: Potti was one of our most important rising stars.

A lot of people were pleased that it was Dr. Potti who made the discovery of a lifetime. Born in India, he was known as an earnest, modest, hardworking Rhodes scholar, who did research at the University of North Dakota before reaching Duke in 2003. He was a young man with a big idea, which he explained in an interview for Duke.

[Potti: And that's the goal, is to...is to be able to tell a patient with cancer that I'm not just a cancer doctor, I'm here to treat your particular cancer.]

Dr. Potti made the breakthrough in the renowned lab of Dr. Joseph Nevins. The Nevins Lab had built a reputation for important work. Dr. Nevins saw something in Dr. Potti and he chose the young researcher to mentor and support.

Nevins: Very bright, very smart individual, very capable. He was a very close colleague to many, many people.

Pelley: And to you.

Nevins: And to me.

When Dr. Potti decoded the genetic makeup of hundreds of tumors, the research created huge computer files of data. That data was the underlying proof in research papers under the names of Potti and Nevins that were a sensation in the top medical journals.

Kevin Coombes: It was going to change medicine. It was gonna change how we treat patients.

Doctors everywhere were eager to save lives with the new discovery. At MD Anderson Cancer Center in Houston, Kevin Coombes and Keith Baggerly began analyzing Dr. Potti’s data to verify his results.

Pelley: And as you dug into the data, what did you find?

Keith Baggerly: We started some basic processing, and we noticed some things that were really odd that we just couldn’t explain.

Coombes and Baggerly are experts in the kind of data created in Dr. Potti’s research. They emailed their questions to Duke and Dr. Potti admitted a few clerical errors, but he said that new work confirmed his results. Duke moved ahead. Drs. Nevins and Potti applied for patents and started a company to market the process. They and Duke stood to make a fortune. Patients enrolled in the clinical trial so that their tumors could be surgically biopsied to be matched with the best drug. But at MD Anderson, during months of analysis, Baggerly and Coombes kept finding errors that they thought were alarming.

Baggerly: One of the things that was especially disturbing was that these types of errors happened again and again and again. That was far beyond anything that we’d seen.

They suspected Dr. Potti had somehow reversed some of the data and that some of the patients could be getting, not the best drug for their tumor, but the worst.

Coombes: Then you would be giving patients drugs that would definitely not benefit them. So there’s clear, potential for harm there.

 

Pelley: Exactly the opposite of what this was supposed to be.

Baggerly: So– yes. So we wrote them and we said, “This– this– this is a big problem.”

Baggerly and Coombes eventually concluded that Duke’s holy grail was worthless. But Drs. Nevins and Potti disagreed.

Pelley: I wonder why, at that point, you didn’t say, as the director of the lab, “Look, stop. Too many questions. We have to get to the bottom of this.” And put a team together to figure that out.

Nevins: I didn’t feel it ever got to that point. I felt that we had addressed the issues that had been raised.

But that changed when researchers here at the National Cancer Institute said they too were having trouble with the data. Duke suspended the enrollment of patients and asked an outside review committee to analyze Dr. Potti’s discovery. After three months, the review committee concluded that Dr. Potti was right.

Baggerly: My immediate reaction was an expletive, which I will not repeat here.

Coombes: We’d gone through the usual channels. We’d written letters to journals. We’d written the article. We’d succeeded in getting the trial suspended, and somebody investigated it. We’d done everything we could.

Duke restarted the clinical trials. And that’s when Juliet and Walter Jacobs sat down for their first meeting with Dr. Potti.

[Walter Jacobs, audio recording: I'm recording this with your permission.

Potti: Absolutely. That's a good thing 'cause you're gonna miss a lot.]

The Jacobs were told, based on the research, that the chances of finding the right drug were approximately 80 percent. Walter Jacobs says no one mentioned that the clinical trial had been suspended because of so many questions.

[Potti: I will help you. Trust me.]

Many trusted because Dr. Potti’s work had been vindicated. But there was just one more thing – discovered, not by a scientist, but by Paul Goldberg, the editor of a small independent newsletter called “The Cancer Letter.” Goldberg got a tip from a confidential source: check Dr. Potti’s Rhodes scholarship. It was right there on his applications for federal grants. Trouble was it wasn’t true.

Pelley: You asked him about it?

Nevins: Certainly I asked him about it.

Pelley: What did he say?

Nevins: He said that while it wasn’t the Rhodes scholar as we know the Rhodes scholar, it was a fellowship from Australia from a group of Rhodes scholars in Australia. So, a stretch of the truth.

Pelley: Was that the moment when you realized?

Nevins: Amazingly, I was still hanging on to the notion of “there must be a good explanation here.” This was–

Pelley: Why were you deluding yourself at that point in time? What is it that you want to believe?

Nevins: I want to believe that somebody that I had trusted, that was a colleague for the last four, five years, someone that I viewed as a friend, was who I thought they were. And then you’re faced with the reality of you’ve been deceived.

Fearing that reality, Joseph Nevins, whose own reputation was at stake, reviewed the original data which had justified the clinical trials for 112 patients. Dr. Nevins discovered that when the underlying data disproved Dr. Potti’s theory, the data were changed.

Nevins: It became clear that there was no explanation other than there was a manipulation. A manipulation of the data, a manipulation of somebody’s credentials and a manipulation of a lot of people’s trust.

Pelley: Manipulated data? These were not errors?

Nevins: That’s correct, it simply couldn’t be random. It simply couldn’t be inadvertent. It had to have been based on a desire to make something work.

Pelley: Is it a close call? Or is it abundantly clear that the data were fabricated?

Nevins: Abundantly clear.

Pelley: When you switch the data, the theory is proved. If you put the data back the way it’s supposed to be, the theory fails.

Dr. Rob Califf: The theory’s a dud if you put the data back to where– the way it was supposed to be.

Pelley: How could that switch happen?

Dr. Rob Califf: If it happened by chance, it would be roughly equivalent to an asteroid hitting the earth.

Duke University agreed to tell us this story as a cautionary tale for other institutions. Vice Chancellor Rob Califf is implementing new procedures for Duke and also overseeing the retraction of Dr. Potti’s papers from the medical journals, one of the most significant retractions in medical history. He’s examining how both a prestigious university and outside investigators missed all the warning signs.

Pelley: How could they have found nothing wrong, nothing suspicious about the work at that point?

Califf: They were analyzing a data set that had been prepared by Dr. Potti. So, the data set they got was one that produced the same results that had been seen in our own analyses.

Pelley: You know there are people watching this interview who are thinking to themselves, “Look, they stood to be wealthy. The university stood to make a lot of money. No one wanted to believe that this research was corrupt.” To what extent was that the reason that the warning signs were overlooked?

Califf: In my view, it was not the money that was the primary driver, it was this great opportunity to help people that was driving people to say, you know, we’ve got to make this work because it looks so good.

Pelley: The patients were told that there was an 80 percent chance that precisely the right drug for their tumor would be found. That wasn’t true. Do you bear any responsibility for that?

Nevins: I regret that some of the issues that were raised along the way I didn’t recognize earlier, and that this could have been brought to a halt at an earlier time.

Juliet Jacobs died three months after she entered the clinical trial. Walter Jacobs and eight others have filed suit. In his answer to the Jacobs lawsuit, Dr. Potti says he was “not aware that false or ‘improper’ information had been included in the research.” Duke has apologized for the trials. And even though the patients hoped that they were getting an innovation that could save their lives, Duke says no one was really harmed because all of them received the standard of care in chemotherapy.

Jacobs: They did not advertise this as a standard of care program, they advertised this as an advanced clinical trial with great results. For what happened to my wife, I have to blame Potti and anyone else associated with him who knowingly promoted a false counterfeit clinical trial exploiting human beings.

Dr. Potti resigned from Duke. He faces an investigation into research misconduct. He told us, in an email, that it would be inappropriate for him to comment. He wrote, “My primary concern at all times is and will be the care of patients and seeking new ways to treat cancer.” These days, he’s working as a cancer doctor in South Carolina. And if you look online, you will see that he is celebrated for “his significant contribution to the arena of lung cancer research.” The websites were created with the help of an online reputation consultant, perhaps to put the best face on the available data.

New Patent Promises to Accelerate Cancer Trials

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Posted 21 Feb 2012 — by James Street
Category Clinical Trials, Individualized treatment, Moffitt Cancer Center, Personalized, Targeted Cancer Therapy

Computer system IDs suitable patients, helps new drugs reach market faster

TAMPA, Fla., Feb. 14, 2012 /PRNewswire/ – A new patent has been issued to Moffitt Cancer Center for a computerized system that efficiently selects the right patient for the right clinical trial. The newly patented system matches the registered patient’s own molecular profile – warehoused in a database of thousands of patient-donated biological tissue or tumor samples – to the molecular design of the drug aimed at targeting their disease at the molecular level, and do it quickly. The system promises to accelerate clinical trials and help shorten the time that it takes to get critically needed new drugs into the market.

Getting new drugs to market to fight cancer and other serious diseases requires, on average, 15 years. The drug development process is long and complex, but the three-phase clinical trials process – estimated to take up to half of those 15 years – is often the bottleneck in getting innovative drugs to the patients who need them.

Clinical trials, increasingly becoming more expensive, are also multifaceted. While patients may qualify for a clinical trial based on their age or stage of disease, they may not be, over the long term of the trial, the best candidates to test a drug. Adverse events, changes in a patient’s health status and the potential for a drug not being effective for them slow the process. Although patients may have met the trial protocol’s criteria, the drug may not be right for them because their molecular profile is not a good match for the chemical and molecular properties of the drug.

Because the concept of personalized medicine is selecting the right drug for the right patient, innovations have been needed to bring personalized medicine to reality. Personalizing the selection process for clinical trials is a vital step.

With the development of new and better ways to examine and understand a tumor’s molecular profile, matching the right patient to the right clinical trial becomes increasingly important. But handling the massive data evaluation necessary to accomplish this has been a stumbling block.

The newly patented computer system, Patent Number US 8,095,389 B2, or “Computer Systems and Methods for Selecting Patients for Clinical Trials,” is designed to surmount that problem.

The newly patented computer system is designed to:

  • Select patients to clinical trials matching an individual’s/drug’s molecular profile
  • Match patients to clinical trials by a patient’s disease/diagnosis
  • Match patients to clinical trials by their symptoms
  • Match patients to clinical trials by their demographic information and family history
  • Track a clinical trial participant’s disease progression compared to drug efficacy

The newly patented computer system and associated products, such as operating system, software, interfaces and data retrieval system, improve clinical trial selection efficacy by making the patient selection process less random and more selective. The technology has the potential to refine clinical trials by eliminating bottlenecks, overhauling the selection process and shortening the timeline, ultimately bringing new drugs to market more efficiently.

About Moffitt Cancer Center

Follow Moffitt on Facebook: www.facebook.com/MoffittCancerCenter
Follow Moffitt on Twitter: @MoffittNews
Follow Moffitt on YouTube: MoffittNews

Located in Tampa, Moffitt Cancer Center is a National Cancer Institute-designated Comprehensive Cancer Center, a description that recognizes Moffitt’s excellence in research and contributions to clinical trials, prevention and cancer control. Moffitt is also a member of the National Comprehensive Cancer Network, a prestigious alliance of the country’s leading cancer centers, and is listed in U.S. News & World Report as one of “America’s Best Hospitals” for cancer.

Media release by Florida Science Communications: www.sciencescribe.net.

SOURCE Moffitt Cancer Center

Introducing ATCC Tumor Cell Panels: Powerful New Tools for Cancer Research

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Posted 18 Feb 2012 — by James Street
Category Biomarkers, Diagnostic, Drug Testing, General Cancer Research, genetic research, Online Research Tools, Open Source Drug Discovery, Tumor biomarkers

PRWeb

Tuesday, February 7, 2012

ATCC launches valuable and gentically-diverse tumor cell panels for drug discovery, pathway analysis and functional genomics

Manassas, VA (PRWEB) February 07, 2012

Searching for appropriate tumor cell models often entails a time-intensive review of the literature and genomic databases. To enable cancer researchers, ATCC (American Type Culture Collection) has introduced a collection of Tissue-Specific Tumor Cell Panels. These powerful new tools combine well-characterized adherent cell lines that were selected for their genomic mutations as found in the Sanger COSMIC database, greatly reducing the time and effort scientists devote to finding these cells. Working closely with customers, ATCC scientists have identified cell lines that that are easy to grow using standard media formulations and possess critical genetic abnormalities found in tumors.

Each Tissue-Specific Tumor Cell Panel is comprised of different cell lines that have been grouped by tissue of tumor origin. In developing the panels, ATCC scientists evaluated 20 different genes associated with tumorigenesis, including TP53, CDKN2A, BRAF, and KRAS. Descriptive information for each cell line has been annotated with details regarding known mutations in these selected oncogenes or receptors. Cell panels, as research models, are as valuable as the depth of understanding and data supporting them. There are currently 10 Tissue-Specific Tumor Cell Panels in the collection, including panels for breast cancer, triple-negative breast cancer, lung cancer, ovarian cancer, colon cancer, liver cancer and pancreatic cancer.

As part of its mission, ATCC will continue to augment the available information on the Tumor Cell Panel cell lines from other databases, and will perform further characterization on the panels. When combined with the size and scope of the ATCC tumor cell line collection, this growing knowledge base enables scientists to make smarter choices when selecting cell-based research models for cancer research, drug discovery, compound screening, biomarker selection, pathway analysis and functional genomics.

“Scientists are requiring more genomic and proteomic data on the cell lines they use in their studies to understand the roles that genetic defects have in the pathobiology of cancer,” said Dr. Richard Kolodner, Member, Ludwig Institute for Cancer Research, UC San Diego School of Medicine Branch. “ATCC is helping scientists by consulting with researchers and going through the gigabytes of data and stacks of literature to find relevant cell lines with sufficient genetic diversity to create a representative panel,” he added.

ATCC Tissue-Specific Tumor Cell panels offer economy over individual lines, are supplied with comprehensive genetic profile information, and are accompanied by expert support if needed.

For more information, please go to www.atcc.org/tcp. To speak with an expert or place an order, call toll free 1-800-638-6597 (option 2) in the U.S. and Puerto Rico, or international callers can dial +1-703-365-2700, or e-mail ATCC Customer Service at sales(at)atcc(dot)org.

ABOUT ATCC
ATCC maintains the largest and most diverse biorepository in the world. The innovative, not-for-profit organization develops and provides products for life science research, services to support biotechnology development, and standards that are consistent with its mission – to acquire, authenticate, preserve, develop, and distribute standard reference microorganisms, cell lines, and related materials for research in the life sciences. With distribution to more than 140 countries and a working relationship with 12 distribution partners, ATCC has the experience, knowledge, rigorous methodologies, standards, longevity and the global reach to serve academic institutions, government agencies, biotech, biopharma, and research organizations around the world.

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For the original version on PRWeb visit: www.prweb.com/releases/prweb2012/2/prweb9174250.htm

http://sfgate.com/cgi-bin/article.cgi?f=/g/a/2012/02/07/prweb9174250.DTL

December 19, 2011 Monday – 11:50 am EST inShare 1 Text Size Smaller Normal Larger E-mail Print ‘Fantastic Potential’: Researchers Keep Cells Alive Away From Body

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Posted 20 Dec 2011 — by James Street
Category Diagnostic, Personalized, Stem Cell Research, Targeted Cancer Therapy

December 19, 2011 Monday – 11:50 am EST

By Adam Daley

Georgetown researchers say they have just significantly changed biomedical research.

Researchers know that normal cells don’t last long once removed from a human, dividing only a few times in a laboratory setting. Common cancers won’t grow in a lab.

That’s about to change.

Senior investigator, Richard Schlegel, M.D., Ph.D., and chairman of the department of pathology at Georgetown Lombardi Comprehensive Cancer Center, has discovered a way to keep normal cells as well as tumor cells taken from an individual cancer patient alive in the laboratory. The technique could be a critical advance, ushering in a new era of personalized cancer medicine, and has potential application in regenerative medicine.

“Because every tumor is unique, this advance will make it possible for an oncologist to find the right therapies that both kills a patient’s cancer and spares normal cells from toxicity,” said Dr. Schlegel. “We can test resistance as well chemosensitivity to single or combination therapies directly on the cancer cell itself.”

The research team found that inserting a Rho kinase (ROCK) inhibitor and fibroblast feeder cells to cancer and normal cells in a laboratory pushes them to morph into stem-like cells. The cells visibly changed their shape as they reverted to a stem-like state.

“In short, we discovered we can grow normal and tumor cells from the same patient forever, and nobody has been able to do that,” said Dr. Schlegel. “Normal cell cultures for most organ systems can’t be established in the lab, so it wasn’t possible previously to compare normal and tumor cells directly.”

“Today, pathologists don’t work with living tissue. They make a diagnosis from biopsies that are either frozen or fixed and embedded in wax,” added Dr. Schlegel. “In the future, pathologists will be able to establish live cultures of normal and cancerous cells from patients, and use this to diagnose tumors and screen treatments. That has fantastic potential.”

The study, which was funded by grants from the National Institutes of Health, Department of Defense fellowship funding, and an internal grant from Georgetown Lombardi’s Cancer Center Support Grant from the National Cancer Institute, is published online today in the American Journal of Pathology.

National Cancer Institute says cancer data at Louisiana Tumor Registry meets top standards

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Posted 20 Nov 2011 — by James Street
Category Bioinformatics, Tumor biomarkers

THE ASSOCIATED PRESS

  • First Posted: November 19, 2011 – 4:01 am

NEW ORLEANS — For the second year in a row, the National Cancer Institute has given the Louisiana Tumor Registry top marks for data quality.

The LSU Health Sciences Center New Orleans says it’s one of four nationwide that met all 16 standards set by the institute’s Surveillance, Epidemiology and End Results Program, which recognizes 17 registries around the country.

Cancer registries collect data including tumor type, stage of disease, treatment, and demographic information. The data often provides clues for research into the causes of cancer.

This is the Louisiana registry’s third top award from SEER.

The Registry includes the central office located at LSU’s school of public health in New Orleans and eight regional offices. The regional offices collect the data. The central office consolidates, processes, edits, compiles, and analyzes the data.

Rational Therapeutics: Intelligent selection of drug combinations

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Posted 17 Nov 2011 — by James Street
Category Drug Testing, Individualized treatment, Personalized, Rational Therapeutics, Tumor biomarkers
Dear Subscriber, BODY LICNovember marks Lung and Pancreatic Cancer Awareness month. Both these diseases typically remain undetected until the cancer has spread. With comparatively low response rates to treatment, both of these diagnoses are generally associated with unfavorable survival statistics.

With this as a backdrop, these two diseases have provided some of our most striking successes. The recent Comedy Night Fundraiser hosted by Stevens Steak & Seafood House to benefit the Vanguard Cancer Foundation provided the opportunity to invite many of our long-term survivors onto the stage for recognition and a photo opportunity.

 

As I looked about the room, I could count among the attendees, lung cancer patients, many of whom are now five or even 10 years since their original diagnoses. Those who are not in the field of medical oncology might not be familiar with the survival statistics for this disease, but I assure you that the words “long-term” and “survivorship” are rarely found in the same sentence as lung cancer.

 

BODY LIC

Dr. Nagourney with some of the long-term lung cancer survivors in attendance at the “Laughter is Contagious” event.

 

While advances in this disease include the discovery of genetic targets for the newest agents like erlotinib (Tarceva) and crizotinib (Xalkori), many of the patients joining us that evening have benefited from more conventional chemotherapy drugs. This only further reinforces our belief that the intelligent selection of therapy can improve outcomes, even without the addition of new classes of therapeutics.

 

Good outcomes in cancer do not necessarily reflect the addition of a new drug or combination, but instead, what can occur simply through the intelligent application of available diagnostic, therapeutic and supportive measures towards the greatest good for each patient.

 

Our provision of assay-directed therapy represents an important step forward in the use of anti-cancer drugs. As we continue to confront hurdles in providing these services to the largest number of patients possible, the support and sponsorship of the Vanguard Cancer Foundation remains an integral part of our mission. With our ongoing efforts to develop the next generation of effective therapies, we look forward to providing our discoveries to patients, regardless of their ability to pay.

 

We look forward to a new year, and to continuing our mission of “Hope Practiced Here.”

Dr. Nagourney Signature
Dr. Robert Nagourney
Rational Therapeutics

SNaPshot: Screening for Many Mutations at Once

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Posted 12 Nov 2011 — by James Street
Category ALK, EGFR, Gene sequencing, genetic research, KRAS, Lung Cancer, Personalized, Tumor biomarkers

Zosia Chustecka

November 11, 2011 — Sending off a tumor sample for a broad screening of genetic aberrations, instead of just a single test, increases the chance of finding a therapy that the patient will respond to, and it might also improve survival, say researchers from Massachusetts General Hospital (MGH), in Boston, who are already using the screen in routine clinical practice.

The broad genetic screen, known as SNaPshot, is advertised around the hospital with a poster that depicts a fingerprint, declaring: “Our patients are unique. So are their tumors.”

The screen can test for more than 50 well-known mutation sites (hot spots) in 14 key cancer genes, and has a turnaround time of less than 3 weeks.

“To our knowledge, we are the first center to offer this broad multiplexed genetic screening to all nonsmall-cell lung cancer [NSCLC] patients,” said Lecia Sequist, MD, MPH, a thoracic medical oncologist at MGH and assistant professor of medicine at Harvard Medical School. She is first author of a paper that reports on the use of the screen in 552 patients with NSCLC, published online November 9 in the Annals of Oncology.

Broad Screen Found Extra Patients

Up to now, genotyping strategies have typically homed in on 1 genetic mutation; for example, lung cancer patients are tested for the epidermal growth-factor receptor (EGFR) gene to identify those who will respond to the EGFR inhibitors erlotinib and gefitinib.

However, “employing a broad gene panel enabled us to provide a therapeutic alternative to lung cancer patients whose tumors harbored much less frequent genetic abnormalities, such as mutations in PIK3CA and BRAF or rearrangements in ALK,” explained senior author Dora Dias-Santagata, PhD, director of the Translational Research Laboratory at MGH.

“These individuals accounted for about 10% of our patient population, but they would have remained ‘invisible’ in the absence of a comprehensive genotyping panel, like the one used here,” she said in a statement.

Identifying these genetic aberrations allowed the researchers to offer patients treatment with targeted therapies that act specifically on those aberrations, which increases the likelihood that the patient will respond to treatment. “Choosing the right therapy can raise response rates in NSCLC patients from around 20% to 30% to 60% to 70%, and may improve survival,” Dr. Sequist said

Use in Other Cancers

The team is currently offering the screening to patients with other solid tumors, such as colorectal and breast cancers, and gliomas, and they are planning to extend the analysis to hematologic malignancies.

“Our study is exciting because it demonstrates that it is possible today to integrate testing for multiple genetic biomarkers in a busy clinic and steer patients toward personalized therapies,” Dr. Sequist explained.

“My message to oncologists is that now is the time to begin thinking about how best to work with pathology — as well as surgery, radiology, and pulmonology — colleagues, to try to adapt their practice toward broad-based genotyping,” she told Medscape Medical News.

“It is something that can be done at most hospitals. We, as a field, need to update our diagnostic practices to accommodate this important test,” Dr. Sequist added.

Pioneering Work

This is a superb initiative.

“This is a superb initiative,” said Jean-Charles Soria, MD, PhD, current president of the European Society for Medical Oncology. This group at MGH is a pioneer in this field, and has “accomplished a tour de force by offering this comprehensive analysis to all their NSCLC patients since 2009,” he told Medscape Medical News.

Although ahead of the game, this work is not entirely unique, he said. A similar approach is being developed at many other large cancer centers, including the Dana-Farber Cancer Institute in Boston; the University of Texas M.D. Anderson Cancer Center in Houston; The Royal Marsden in London, United Kingdom; Val d’Hebron in Barcelona, Spain; and his own center, Institute Gustave Roussy in Villejuif, France.

Medscape Medical News has previously reported on the broad-screen genotyping carried out at M.D. Anderson and by the Lung Cancer Mutation Consortium, which involves 14 centers in the United States. However, these initiatives are focused on enrolling patients in clinical trials, whereas the MGH team is using their broad screen in routine clinical practice.

“This approach will become standard practice in all major academic centers in Europe and North America…in 3 to 5 years at most, in my opinion,” Dr. Soria predicted.

At the moment, this approach belongs in academia and large care centers, said Alex Adjei, MD, a thoracic oncologist who is senior vice president of clinical research and professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York. He agrees that broad-based genotyping is something that oncologists need to think about, but argued that this approach is not ready for widespread use. “It will become relevant to community oncologists, but that is a few years away,” he told Medscape Medical News.

Dr. Adjei explained that, at the moment, the main problem with this approach is that a lot of the information obtained is of academic interest and has little practical relevance. There are currently only a few targeted drugs available that home in on genetic aberrations. Although there are many under development, the only way to get a patient on these is to enroll them in a clinical trial, which best done in academic hospitals and large cancer centers, he said.

It makes sense to screen for many different mutations and genetic aberrations all at once, rather than one at a time, but for this approach really to come into its own, “we need to have more drugs available,” he said.

Right now it’s not ready for general use.

“For this to become routine and for this to make sense, we have to have more actionable mutations,” he said. “There is no point looking at 15 genes and finding 50 mutations when you can treat only a few of them.”

“SNaPshot is a great idea and has great utility because it is going to simplify molecular testing. This is the way of the future, but right now it’s not ready for general use,” Dr. Adjei concluded.

A slightly different opinion comes from community oncologist Patrick Cobb, MD, from Billings, Montana. Some practices are sending off tumor samples for broad genotyping. “It is already starting to happen at the community level,” he said.

“It is relevant to us,” he explained. Community oncologists are having to keep up with research and to change their practices accordingly, Dr. Cobb said. It is already standard practice to test colorectal cancer for KRAS (and BRAF) mutations and to use Oncotype Dx in breast cancer. These test results are influencing treatment decisions, and sparing some patients unnecessary adverse effects, he said. His own practice is considering EGFR and ALK testing for lung cancer, but hasn’t done so yet; however, they are testing melanoma for BRAF mutations.

“There’s much more collaboration nowadays between medical oncologists and pathologists,” Dr. Cobb said. “We’ve always been tied at the hip,” but in recent years, with pathologists providing information on mutations as well as histology, that collaboration has intensified.

“As an oncologist, this is an exciting time. We are really seeing the benefit of bench research starting to affect the way we are treating our patients,” he said.

Between the top academic centers and community practices are the middle-sized hospitals. Curtis Miyamoto, MD, is a professor of radiation oncology at just such a hospital — Temple University Hospital in Philadelphia, Pennsylvania. He thinks that “this broad genetic testing will be mainstream in the future, probably 5 years from now, but it’s not mainstream yet.”

“SNaPshot is great idea,” Dr. Miyamoto told Medscape Medical News, “and I do think it will become a standard of care in the future…. It provides valuable information that can change the way a patient is treated and can make a big difference, especially for patients who are being treated nonspecifically and who may be missing opportunities to get well because they are not getting the testing done.”

However, such genetic testing needs to be placed in the larger picture of strained healthcare resources and decreasing investment in new drug development, he said. “It’s very nice to have these profiles, but what about the drugs to treat patients with these results?”

Dr. Miyamoto echoed the point made by Dr. Adjei — that for many of the mutations, targeted drugs “are not available yet…. How many will be developed under the current financial constraints…, and further down the line…, will we be able to afford to use them?”

First Cohort of Patients

In their paper, the MGH team reports on the first cohort of NSCLC patients screened with SNaPshot. A total of 589 patients were referred for genotyping, and 95% of these (n = 552) had sufficient tumor tissue for the screen.

The median age of the patients was 64 years (range, 22 to 89), 58% were female, and 92% were white, “reflecting our clinic’s racial homogeneity,” the researchers write. Histology was predominantly adenocarcinoma (81%), and about a quarter of the patients (24%) were never smokers.

The screen identified driver mutations in 51% of the patients. Most of the tumor samples had 1 mutation, but 5% had 2 mutations, and 2 tumors had 3 mutations.

The most commonly occurring mutations were KRAS (in 24% of tumor samples), EGFR (in 13%), and translocations involving ALK (5%).

There is wide agreement that it is important to identify patients with EGFR and ALK aberrations, the researchers note, because targeted therapies directed at the aberration (erlotinib and gefitinib for EGFR and crizotinib for ALK) are available.

There are also data that support directing patients with certain genotype findings “away” from therapies; for example, patients with KRAS mutations are directed away from erlotinib.

In addition, there are investigational therapies aimed at some of the other mutations that were found (such as MRK inhibitors for KRAS mutations), and therapies that are aimed at BRAF, PIK3CA, and HER2 mutations.

Of all the patients with genotypes, 22% have begun treatment with a genotype-specific therapy in response to SNaPshot results, the team reports.

Determining the percentage of these patients who would have received targeted therapy in the absence of SNaPshot is difficult, “because it would depend on whether any genetic testing was being done, and if it was, how much,” Dr. Sequist told Medscape Medical News.

Two steps are required before patients receive genotype-specific therapy: “step 1 is doing the testing and step 2 is having the drugs available,” she explained. “I think it is fair to say that EGFR mutation testing is fairly routine in most places around the world currently, and ALK testing is becoming more and more common because the new ALK inhibitor crizotinib has been approved by the US Food and Drug Administration in the United States. As the portfolio of drugs that target these various cancer mutations expands, not only through clinical trials but also through new drug approvals, there will be more of a pressing need to make broad genotyping the standard clinical practice of oncology. Our paper is important because it shows that this type of broad testing can be woven into the everyday care of patients already,” Dr. Sequist said.

What about the clinical outcomes of patients who are identified on screening and are then treated with targeted therapies?

“The field of targeted cancer therapy is still in its infancy, Dr. Sequist told Medscape Medical News. “At the current time, we have not seen that targeted drugs can cure cancers that were not curable otherwise. However, it is likely that survival can be lengthened by these types of treatments. Although not addressed in [our Annals of Oncology paper], our group recently published a study demonstrating that ALK-mutated patients receiving the ALK inhibitor crizotinib survived longer than ALK-mutated patients who did not get the drug” (Lancet Oncol. 2011;12:1004-1012). These data on crizotinib were previously reported by Medscape Medical News.

“We are getting much smarter in treating cancer, and focusing on these genetic changes and using targeted therapies is getting us closer to the ideal of personalized medicine,” said Dr. Cobb.

We are confident that these breakthroughs will make a difference in outcomes for patients, he noted. “There is really no reason why they shouldn’t, but we haven’t really proven that,” Dr. Cobb told Medscape Medical News. “To prove it, you have to marry what we see in the lab with what happens in the patient.”

There is a precedent here that bodes well for the future of this approach. Already in breast cancer, targeting treatment (tamoxifen to estrogen-receptor status and trastuzumab to HER2-receptor status) has led to a marked improvement in survival and cure rates, Dr. Cobb explained. However, this level of data is not available yet for treatment modified according to genetic mutations, he said.

“I don’t think anybody thinks that this is not going to be important,” he added. “There’s plenty of excitement about it; we just haven’t proven it yet.”

Dr. Sequist reports consulting for Clovis Oncology, Merrimack Pharmaceuticals, Daichi-Sankyo, and Celgene. Dr. Dais-Santagata and her colleague at the Translational Research Laboratory at MGH, John Iafrate, MD, PhD, have submitted a patent for the SNaPshot tumor genotyping assay. Dr. Soria reports receiving honoraria from Abbott, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, Merck, MSD, Servier, sanofi-aventis, and Eli Lilly. Dr. Adjei has disclosed no relevant financial relationships.

Ann Oncol. Published online November 9, 2011. Abstract

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