The Future of Cancer Research Lies Behind Us

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The TED (Technology Entertainment Design) conferences have been held annually for almost two decades. It draws together innovators in a broad spectrum of disciplines. With invited speakers ranging from Harvard's Edward O. Wilson to business leaders like Microsoft's Bill Gates, the lectures cover a panoply of interesting topics.

Dr. Robert Nagourney was invited to present at the TEDxSoCal conference held in Long Beach, CA on July 16th. His interest was to engage this group in a discussion of cancer biology with the focus on biochemistry and metabolism. His lecture was timely in the context of the New York Times article on the failures of genomics platforms for cancer treatment.

Over the past year, there has been a growing recognition that genomic analyses are not providing the therapeutic insights that patients so desperately need. The Duke University lung cancer gene program, which received much attention, is emblematic of the hubris associated with contemporary genomic analytic platforms.

Dr. Nagourney has reviewed the contemporary experience in clinical trials, examined the potential pitfalls of gene-based analysis, and described the brilliant work conducted by biochemists and cell biologists, like Hans Krebs and Otto Warburg, who published their seminal observations decades before the discovery of the double helix structure of DNA.

He described insights gained using the cell-based funtional profiling analytic platform, that lead to treatments used today around the world, all of which were initially discovered using cell-based studies. More interesting still will be the opportunity to use these platforms to explore the next generation of cancer therapies - those treatments that influence the cell at its most fundamental level - its metabolism.

http://www.youtube.com/watch?v=mAGhNhrHMJs

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Research in Combining Targeted Agents Faces Numerous Challenges

In a conference sponsored by the Institute of Medicine, scientists representing both public and private institutions examined the obstacles that confront researchers in their efforts to develop effective combinations of targeted cancer agents.

In a periodical published by the American Society of Clinical Oncology (ASCO) in their September 1, 2011 issue of the ASCO Post, contributor Margo J. Fromer, who participated in the conference, wrote about it.

http://www.ascopost.com/articles/september-1-2011/research-in-combining-targeted-agents-faces-numerous-challenges.aspx

One of the participants, Jane Perlmutter, PhD, of the Gemini Group, pointed out that advances in genomics have provided sophisticated target therapies, but noted, "cellular pathways contain redundancies that can be activated in response to inhibition of one or another pathway, thus promoting emergence of resistant cells and clinical relapse."

James Doroshow, MD, deputy director for clinical and translational research at the NCI, said, "the mechanism of actions for a growing number of targeted agents that are available for trials, are not completely understood."

He went on to say that the "lack of the right assays or imaging tools means inability to assess the target effect of many agents." He added that "we need to investigate the molecular effects . . . in surrogate tissues," and concluded "this is a huge undertaking."

Michael T. Barrett, PhD, of TGen, pointed out that "each patient's cancer could require it's own specific therapy." This was followed by Kurt Bachman of GlaxoSmithKline, who opined, "the challenge is to identify the tumor types most likely to respond, to find biomarkers that predict response, and to define the relationship of the predictors to biology of the inhibitors."

What they were describing was precisely the work that clinical oncologists involved with cell culture assays have been doing for the past two decades. One of those clinicians, Dr. Robert Nagourney felt that there had been an epiphany.

The complexities and redundancies of human tumor biology had finally dawned on these investigators, who had previously clung unwaiveringly to their analyte-based molecular platforms.

The molecular biologists humbled by the manifest complexity of human tumor biology had finally recognized that they were outgunned and whole-cell experimental models had gained the hegemony they so rightly deserved.

Source: Dr. Robert A. Nagourney, medical director, Rational Therapeutics and instructor in Pharmacology at the University of California, Irvine School of Medicine. He posted about this on his blog.

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Symposium on Circulating Tumor Cells and Chemosensitivity Testing
Santa Monica, December 7-9, 2011

Robert Nagourney, MD, founder of Rational Therapeutics, Inc., Long Beach, CA, was a featured speaker at The Symposium on Circulating Tumor Cells and Chemosensitivity Testing, December 7 - 9, at Loews Beach Hotel, Santa Monica, CA.

The academic conference was sponsored by the Angeles Clinic Foundation, as a result of a generous gift from the Farrah Fawcett Foundation. Fawcett died in 2009 at St. John's Health Center after a lengthy battle against cancer, but was a believer in what is being called Personalized Cancer Cytometrics -- a decision by investigators in the field, who decided that they should actually come up with a name which everyone will agree to use.

This was the first symposium of it's kind to be offered in the world and the development of this type of technology was the hope and dream of Farah Fawcett whose foundation has supported the development of this symposium. Ms. Fawcett had chemotherapy through the John Wayne Cancer Institute of which The Angeles Clinic is affiliated.

The invitation only symposium brought together the world's prominent researchers in this area in order to raise awareness and explore current methods of cancer treatment including assays. Although the symposium was a very closed affair, a formal "White Paper" is being produced and a there may be a formal peer-reviewed publication coming out of it.

Dr. Nagourney, a board certified oncologist and hematologist and noted expert on chemosensitivity testing for more than 20 years, will highlight the lack of progress made in this arena due in part to the politics and economics of cancer treatment. "Physicians tend to follow standardized guidelines or ‘off the shelf treatments' that provide the same traditional chemotherapy agent to every cancer patient. The treatments work adequately well, the schedules are established, the toxicities are well known, and no one is cured."

Dr. Nagourney, who recently addressed the situation at a TEDx symposium, sees an overwhelming need to spread the message this conference addressed - using cell-death cell culture assays, which provide a functional profile of how the cancer will respond to treatment.

Dr. Nagourney says, "Combining diagnostic skill with scientific insight, the physician becomes the captain of the ship." He adds that assay-directed approaches can provide objective data that is then used to guide treatment selections. "Predicated upon an understanding of the patient's tumor biology, cancer therapy becomes an intellectual exercise that draws upon literature and a knowledge of pharmacology and physiology," he says.

HealthNewsDigest.com

As there had been a death in my family, my ability to attend the entire conference was limited and I could only particpate the afternoon session. The symposium included several areas of investigation, including circulating tumor cell analysis, molecular profiling and functional analytic platforms. I had the opportunity to sit in on several presentations including one by Dr. Weisenthal, who gave an overview of his seminal contributions to the field followed by his discussion of his work on VEGF inhibition and the crosstalk between other classes of tyrosine kinase inhibitors and endothelial (vascular) cell viability. Dr. Presant gave a presenation on their work with the MiCK assay, with a focus upon leukemia studies and their developing work on solid tumors. My impression is that we made a fundamental transition. In the past I was repeatedly confronted by oncologists who said: ”We could not do this.” Today the question appears to be more: “How best can we do this?" In that regard there has been progress. - Robert Nagourney