Why Hasn’t Functional Profiling Been More Broadly Accepted in the United States?

This is an interesting question. One that my colleagues in the field and I have often pondered. Is it that American medicine is more conservative than European and Asian medicines? Are we late adopters? Do we hold medical tests and treatments to a higher standard? Are American doctors too wedded to protocol therapies? Is it cooperative groups that guide all of our decisions? NCCN guideline? Pharmaceutical marketing?

Or is it possible that a small number of opinion leaders opted out of the field and have done their best to take everyone else with them?

I would say it is the latter.

In some ways, the slow adoption of these techniques — compared with Europe and Asia — does reflect the relative conservatism of American medicine. We have been slow to adopt acupuncture and incorporate diet and lifestyle changes into medical therapy, despite their manifest importance. We are often slower to improve drugs, even when they establish clinical utility in well-conducted foreign trials. So, there may indeed be a component of late adoption and conservatism.

However, The re-importation of technologies is not only seen in the medical community. The early adoption of transistor technology by the Japanese despite their development by American inventors; the late adoption of robotics and fuzzy logic by Americans; and our tardiness in adopting smaller, more fuel-efficient automobiles all illustrate this point. But, the most vexing hurdle of all has been the dismissal by mostly university-based investigators who have weighed in against the adoption of human tissue tests for the prediction of response to chemotherapeutics.

These investigators — who, in aggregate, provide care to less than 10 percent of the cancer patients in need — have an inordinate amount of influence upon the application of novel technologies. In what can only be viewed as a sour grapes phenomenon, many of these physicians even tried to apply early forms of human tumor study in their own labs and medical centers.

The utter failure of the clonogenic assay in the 70s and 80s and related growth-based technologies, poisoned these academics and closed their minds to newer developments based on the modern discoveries of apoptosis and other forms of programmed call death. When we, and our colleagues, reported discoveries using these more modern endpoints, the academic community turned a deaf ear. As our data improved, they dug in their heels. And when the data rose to the level of the best peer reviewed journals in the field, the critics became ever more vocal.

We can now thank these “scientists” for putting the United States behind Europe and Asia in the adoption of these important methodologies. While patients in America must struggle with their physicians to get ex-vivo analyses conducted, children in Europe with leukemia have immediate access to these tests. Adults in England with leukemia can all request these assays, German patients regularly take advantage of assay methodologies. And the Japanese often apply related techniques for the treatment of their solid tumors.

Not unlike robotics, total quality management and fuel-efficient automobiles, the Americans (who invented in vitro chemosensitivity testing) will again be importing the technology that they are responsible for developing.

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.

3 Responses to Why Hasn’t Functional Profiling Been More Broadly Accepted in the United States?

  1. Nydia Martinez says:

    I was diagnosed with breast cancer this time last year and followed the “standard treatment” with very severe side effects. I wish I would have known about these tests before initiating treatment. I’m glad you’re doing this! My question is, recently I saw on TV a program called Stand Up to Cancer! An attempt to expedite research on cancer cures. I’m wondering if you know whether some of these university-based researchers are involved in this effort and whether you are involved?

  2. Nydia:

    I am distressed to learn of the poor tolerance that you experienced and can only hope that the therapy proved effective. While it is impossible, in retrospect, for us to know whether the EVA/PCD approach would have changed your therapy, we would have been very happy to try.

    As to the SUC 2. We applaued these generous sponsors for their support of cancer research. Every bit of support helps. The problems is that, despite the best intentions, the funds raised more often than not wind up in the hands of the same investigators and institutions that got us in this mess in the first place. While we appreciate the effort, it would be very exciting if these types of support could be directed toward true innovators. Perhaps you could lobby to become a member of the next study section for SUC 3 so that you could be sure that the money raised did the most good.

  3. Gregory D. Pawelski says:

    There is so much misinformation about the cell culture assay technology being perpetuated. All the important progress in the technology has come outside of NCI-sponsored university-based research and it strikes at the heart of the standard NCI/university clinical research paradigms. That’s why some doctors have not yet made the effort to learn about this.

    Because of the efforts of a dedicated private sector and the availability of media such as the Internet, the NCI and NCI-oriented institutions will soon find themselves in the position of having to make the effort to learn and to be forced to provide sound reasons if they choose not to use these tests in the management of individual patients.

    And why is it that some private insurance companies are not paying for this testing?

    The validaton standard that private insurance companies are accepting from molecular profiling tests is accuracy and not efficacy. The ‘bar’ had been instantly lowered. No longer will it be essential to prove that the use of a diagnostic test improves clinical outcomes, all they have to do for these molecular profiling tests is prove that the test has a useful degree of accuarcy. However, the validation standard wanted for functional tumor cell profiling is efficacy. What’s good for the goose is good for the gander.

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