When Fluff Isn’t Enough

Recent press coverage from the San Antonio Breast Cancer Symposium (SABCS) touched upon the development of multi-gene predictors for clinical response in breast cancer. One report from that meeting described correlations between a laboratory assay model in use at the University of Pittsburgh and microarray analyses. However, the suggestion that this laboratory technique — described by its proponents as a chemosensitivity assay — could accurately identify gene profiles that would predict response seems at odds with the current literature.

Although the press coverage concluded that this technique showed “promising performance” it was largely exploratory and defined by the authors as a “validation study.” What is interesting is that a team of highly reputable investigators from M.D. Anderson recently reported a very negative study using a similar approach of identifying target genes in cell lines and then correlating them with patient outcomes. In the paper, published in the June 2010 issue of Breast Cancer Research and Treatment (Liedtke, C. et al. Breast Cancer Res Treat. 2010 Jun; 121(2):301-9) the authors reported “cell line derived predictors of response to four commonly used chemotherapy drugs did not predict response accurately in patients.”

Indeed, differential gene expression seemed only to correlate with paclitaxel. The authors found that false discovery rates were high for all other drugs tested. Thus, the report from the SABCS will need to be carefully examined to determine whether truly relevant clinically predictive information can be provided by this particular laboratory platform.

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.

One Response to When Fluff Isn’t Enough

  1. Tamara Danner Kreisher says:

    Dr Nagourney, thank you for giving hope to the patients who are told there is no hope.

    My Father, Fred will be meeting with you on 2/14/11. I am very appreciative of all the support and guidance Shari Burt has given during this difficult time trying to navigate through the Kaiser process.

    Many Thanks,

    Tamara

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