National Cancer Institute Stops Gene-based Clinical Trials – Part 1

In prior posts we have discussed the clinical potential of genomic profiling for the selection of chemotherapeutics. Although, genomic analyses offer many insights, we described the limitations of these platforms. A recent report in the national media gives further credence to our position.

On July 22 and 23, 2010, the National Cancer Institute suspended two lung cancer and one breast cancer clinical trial that used genomic profiling to select active treatments for patients. The technique applied was developed at Duke University and reported, to much fanfare, in Lancet Oncology in 2007. The rather stunning success reported in this and related articles by the investigators from Duke, lead to a widespread belief that gene profiles would select active therapies for patients.

The first chink in the armor of this argument came when scientific reviewers issued an “expression of concern” regarding the validity of the method. Further analyses revealed evidence that the technologies for the prediction of response in individual patients could not be reproduced. As the reviewers stated, “The scientific community should be able to replicate the results with the reported data available.” They continued, “Having tried, we can confidently state that this is not yet true.” The NCI convened a group of 31 scientists, who concluded, “It is absolutely premature to use these prediction models to influence the therapeutic options open to cancer patients.”

Next week we’ll explore what went wrong with these seemingly promising trials.

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 National Cancer Institute Stops Gene-based Clinical Trials – Part 1

  1. Pingback: National Cancer Institute Stops Gene-based Clinical Trials – Part 2 « Dr. Robert A. Nagourney's Blog

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