Why I Do Chemosensitivity Testing

My earliest experience in cancer research came during my first years of medical school. Working in a pharmacology laboratory, I studied the biology and toxicity of a class of drugs known as nitrosoureas. My observations were published in a series of articles in the journal Cancer Research.

The work afforded me the opportunity to interact directly with some of the country’s leading cancer investigators. Many of the fellows with whom I worked went on to famous careers in academia and the biotech industry. I remember the rather dismal outcomes of patients treated in the early 80s; but I felt confident that there had to be a better way to treat cancer patients than just throwing drugs at them and hoping they worked.

It was then that I decided that testing cancer patients’ cell samples in the laboratory, using the drugs they might receive, could help select the most active agents. Several years later, as an oncology fellow, I had the opportunity to test this hypothesis, and it worked. I reported my first observations in leukemia patients in 1984, a successful study that proved that relapsed leukemia patients could be effectively treated when the drugs were first selected in the laboratory. (Nagourney, R et al, Accurate prediction of response to treatment in leukemia utilizing a vital dye exclusion chemosensitivity technique. Proc ASCO abs # 208, 1984)

Unfortunately, this was an era when the field of in vitro chemosensitivity testing had fallen on hard times. A negative study published in the New England Journal of Medicine, using a growth-based assay endpoint, soured the community on the concept and our cell-death based assay results fell upon deaf ears. Yet, I knew it worked. And, based upon my continued efforts in the field, I developed the EVA/PCD® platform that we use today.

With response rates two to three fold higher than national averages, and successes that include the development for the most widely used treatments for low grade lymphoma and CLL (Nagourney, R et al Br J Cancer 1993), recurrent ovarian cancer (Gyn Onc 2003) and refractory breast cancer (J Clin Oncol 2000), the question really should be why doesn’t everyone do assays for their patients?

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.

4 Responses to Why I Do Chemosensitivity Testing

  1. Pingback: Why I Do Chemosensitivity Testing? by Dr. Robert Nagourney, of Rational Therapeutics « Rational Therapeutics – Hope Practiced Here for Cancer Patients

  2. I was at our weekly clinical conference in Denver at the Extremities at Risk meeting. They deal with soft tissue and bone based malignancies here. There was a difficult case with osteosarcoma I recall, and I raised my hand and asked, Did you send a tissue biopsy to Rational Therapeutics for oncology treatment testing? First of all I was shocked that the moderator had to explain the whole process of invitro testing of chemotherapeutic agents prior to injecting them into the patient. This is a multidisciplinary conference with pathologists, radiologists, orthopedic surgeons, oncologists and plastic surgeons. The moderator who is know nationally mentioned the process in a very brief manner. I think it is just not known wide enough. This method is so common sense to me, I cannot believe this is not the standard of care in oncology. Instead we are “experimenting with our patients” with potentially toxic drugs before we know it will work. I think a patient education campaign would make this a required option for patients. Keep up the good work.

    Paul Battle PA-C
    Barolat Neuroscience
    Grossmand Wellness Clinic

  3. Chemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet.

  4. Pingback: BOOK REVIEW: OUTLIVING CANCER | CANCER STORY

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