If It is Too Good to Be True . . .

The February 12, 2012, CBS 60 Minutes covered a story that has sparked a great deal of interest among cancer patients and medical professionals. The topic was an investigator named Anil Poti who, while working at Duke University developed a laboratory platform for the study of human lung cancer.

Using molecular profiling, Dr. Poti and his collaborators, reported their capacity to distinguish responding and non-responding cancer patients, providing survival curves that were nothing short of astonishing. I recall attending the original lectures given by these investigators at the American Association of Cancer Research meeting several years ago.

As an investigator in the field of drug response prediction, working in lung cancer I had a particular interest in their platform and I was extremely impressed by the outcomes they reported. At the time, I wondered how the static measurement of gene profiles could possibly characterize the nuances of human biology, to encompass the epigenetic, siRNA, pseudogene, non-coding DNA and protein kinetics that ultimately characterize the human phenotype. Nonetheless, with such compelling data I was prepared to be convinced.

That is until a relatively unheralded report in the Cancer Letter raised concerns by several biostatisticians regarding the reproducibility of Dr. Poti’s findings. And then more comments were followed by a full NIH investigation. A panel of biostatisticians was convened and a formal report provided the explanation for Dr. Poti’s excellent results.

They had been invented. The clinical outcomes were not real results. The findings had been retrofitted to match the patient responses and this was the subject of the 60 Minutes report.

What the 60 Minutes report did not address however, was the real problem. That being the inability of contemporary genetic profiling to truly define human biology. For all the reasons enumerated above, siRNA, non-coding DNA, etc., the simple measurement of gene sequences cannot accurately predict biological behavior. This is what the 60 Minutes reporters and the physicians they interviewed, never discussed. The problem at hand is not an errant investigator but an errant scientific community. Our love affair with the gene that began in 1953 (Watson and Crick) has now been confronted by a most heartbreaking example of infidelity (pun intended).

Genes do not make us what we are; they only (sometimes) permit us to become what we are, with the vagaries of transcription and translation lying between.

This leads us to the reasons I find this so critically important:

  1. I cannot stress strongly enough that this is NOT what I do. Genomic analysis (their work) and functional analysis (our work) are distinctly different platforms.
  2. I strenuously resist any attempt on the part of anyone to tar me or my work with this brush.
  3. It is precisely because genomic analysis cannot accurately predict cancer patient outcomes, that these investigators found it necessary to invent their data.
  4. Despite this, functional analyses can and do provide these types of predictive results in lung cancers and other diseases as we have reported in numerous publications.
  5. Finally, while imitation is the sincerest form of flattery, this is one instance in which I would prefer to decline the compliment.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

2 Responses to If It is Too Good to Be True . . .

  1. Pat M says:

    Dr. Nagorney,

    Thank you for so clearly and passionately articulating the difference between what you do and what “they” do. After 3.5 years of preaching to anyone who will listen, I am still struck and saddened by the lack of patient understanding of the differences between tests that could potentially save their lives.

    Most patients have no idea that there are fundamental differences in the kinds of tests that might be used to determine their treatment. They are told by their oncologists that DNA tests or certain blood test or screening test can be used to “personalize” a treatment plan unique to them. What they are not told is that their treatment plan will actually be based on what statistically ended up working for OTHER patients. I can’t think of anything LESS personal than being a statistic. And then to find out, as in the case of Dr. Poti, those statistics themselves were manipulated! No thank you!

    Dr. Nagourny, I don’t care if statistically 99.9% of patients with my same DNA markers would have shown success on any DNA based treatment plan, be it from Duke, MDA or UCLA. All I care about is that YOU took a living chunk of ME, subjected MY tumor tissue to a series of potential drugs, looked into the microscope and counted how many cancer cells dropped dead each time, then gave me the winning drug. My success rate? 100%. The Funtional Profile Assay is the ONLY test that is truely personalized and that every patient, every oncologist AND 60 Minutes should be interested in!

    Gratefully yours, Pat

  2. Dr. Weiss, on cancergrace.org, repeatedly knocks down hopes for chemosensitivity testing by espousing upopular views like pharmakokinetics and pharmacodynamics of the drug, normal host response, tumor micro-envionment, etc., are simply not tested by these assays. The very things that the functional analysis platform actually does and the genomic and proteomic analysis platforms do not.

    And his colleague, Dr. West, thinks it’s always fair to have a good debate about these things and hope we never rely on something being “the party line” as the primary justification for doing or not doing something. He says that people should challenge, while he bans anyone from the site, that challenges their “party line” thinking. He doesn’t think there’s good reason to have much faith in these assays.

    Dr. West states that views expressed on his site represent his opinion, not those of GRACE or Swedish Cancer Institute. His information does not constitute medical advice, while Dr. Weisenthal calls him out for giving medical advice on his site (he advised a patient not to use her assay report out, after she spent the time and money finding the most effective anticancer agents against her individual cancer cells).

    Seems like someone is trying to tar the work of functional profiling analytics.

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