Cancer Research Becomes “Curiouser and Curiouser”

Following the Gina Kolata New York Times article on July 8, 2011, which described the failure of the Duke University gene profile program in lung cancer, a second New York Times article popped up on the radar screen.  “Cancer’s Secrets Come into Sharper Focus” by George Johnson, examined the growing complexity of cancer research.

This article explored the growing realization that human biology is not linear. Included were references to work that we have previously described in this blog, including the groundbreaking work of Pier Paolo Pandolfi. It also described the interaction between the human body and its microbial flora. We have long recognized that human health is, in part, associated with our interaction with microbes in our environment. The gastrointestinal tract has numerous species that are increasingly believed to contribute to our health. The growing field of probiotics, wherein people consume “healthy organisms,” has gone from quackery to community standard in less than a decade.

What is interesting over the past years is the growing recognition that many cancers are related to infections. Viral infections are known to be oncogenic, with the Epstein-Barr virus, HPV and other viruses now known to be causative of lymphomas, cervical, head and neck, and other cancers. The association between helicobacter and ulcers, gastric lymphoma, and esophageal malignancies are of interest both epidemiologically and therapeutically.

What is most interesting of all is the growing recognition that the cancer cell is but a small component of the cancer.

Here at Rational Therapeutics we recognized the interplay between cells, stroma, vascular elements, cytokines, macrophages, lymphocytes and other environmental factors. This lead to our focus on the human tumor primary culture microspheroid, which contains all of these elements. In our earlier work, we endeavored to isolate tumor cells from their benign constituents so as to study “pure” tumor cells. As time went on, however, we found that these disaggregated cells were artificially sensitized to the effects of chemotherapy and provided false positive results in vitro.

Early work by Beverly Teicher and Robert Kerbel that examined cells alone and in 3-dimensional structures, lead to the realization that cancer cells inhabit a microenvironment. Our lab now studies cancer response to drugs within this microenvironment, enabling us to provide clinically relevant predictions to our patients.

It is our capacity to study human tumor microenvironments that distinguishes us from other platforms in the field. And, it is this capacity that enables us to conduct discovery work on the most sophisticated classes of compounds that influence cell signaling at the level of notch, hedgehog and WNT, among other (Gonsalves, F, et al. (2011). An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of WNT/wingless signaling pathway. PNAS vol. 108, no. 15, pp. 5954-5963).  With this clinically validated platform we are now positioned to streamline drug development and advance experimental therapeutics.

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 Cancer Research Becomes “Curiouser and Curiouser”

  1. Linda S says:

    Hi Dr. Nagourney —
    I’d appreciate your take on a subject we discussed on an ovarian support group cancer site a few weeks ago:
    Given that:
    “Here at Rational Therapeutics we recognized the interplay between cells, stroma, vascular elements, cytokines, macrophages, lymphocytes and other environmental factors. This lead to our focus on the human tumor primary culture microspheroid, which contains all of these elements.”

    Is it likely the type of sample submitted for testing (e.g., lymph node, ascites, solid tumor), which one suspects contains differing components, could produce different chemosensitivity results? If so, then how would one best treat using assay results if cancer has recurred in an organ, lymph system AND produced ascites?

    thanks so much, appreciate the open dialogue you generously provide us.

    Linda

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