Breakthroughs In Cancer?

Coco Chanel, the icon of 20th century fashion once said, “Only those with no memory insist on their originality.” I am reminded of this quote as I review recent discoveries in cancer, among them, the recognition that cancer represents a dysregulation of cellular metabolism.

The field of metabolomics (the systematic study of cellular energy production), explored by investigators over the last decade is little more than the rediscovery of enzymology (a branch of biochemistry that deals with the properties, activity, and significance of enzymes), biochemistry (the science dealing with the chemistry of living matter) and stoichiometry (the part of chemistry that studies amounts of substances that are involved in reactions), pioneered by investigators like Albert Lehninger, Hans Krebs, Otto Warburg, and Albert Szent-Gyorgyi. These innovators used crude tools to explore the basis of human metabolism as they crafted an understanding of bioenergetics (the study of the transformation of energy in living organisms) and oxidative phosphorylation (processes occurring in the cell’s mitochondrion that produce energy through the synthesis of ATP (energy carrier of the body).

More recently, scientists wedded to genomics have slowly come to recognize the limitations of their approach and have returned to the field of phenotypic (the observable physical or biochemical characteristics of an organism analysis.

While newcomers to the field claim to be the first to recognize the role of cellular biology in tumor biology, a cadre of dedicated investigators had already charted these waters decades earlier. Beginning with the earliest studies by Siminovitch, McCulloch and Till, subsequent investigations by Sydney Salmon and Anne Hamburger, developed the earliest iteration of cellular studies for the examination of cancer biology in primary culture.

Ovarian Cancer

Ovarian Cancer

The work of Black and Spear, published in the 1950s similarly explored the study of human cellular behavior for the study of cancer research. While Larry Weisenthal, Andrew Bosanquet and others established useful predictive methodologies to study cellular phenotype, their seminal contributions have gone largely unrecognized.

Today, start-up companies are examining cellular biology to predict cancer outcomes, each claiming to be the first to recognize the importance of cell death events in primary culture. The most recent and widely touted in the literature is the use of mouse avatars. Implanting biopsied explants of tissue from patients into nude mice, they grow the cancers to desired size and then inject the drugs of interest to show tumor shrinkage. To the discerning eye however, it obvious that this represents little more than an expensive, inefficient, and extremely slow way to achieve that, which can be done more easily, inexpensively, and quickly in a tissue culture environment.

When I read the promotional material of some of the new entrants to this field, I am reminded of another quote, that of Marie Antoinette, who said, “There is nothing new except what has been forgotten.”

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.

2 Responses to Breakthroughs In Cancer?

  1. Shaker Farhat, MSc, PhD(c) says:

    My colleagues and I enjoy reading your blog and sharing your insights. We hope that in the context of cancer breakthroughs, more may be accomplished by combining the best technologies of genomics, proteomics, phenotypic analysis, etc., together with the power of high tech/supercomputers, and see if this would lead to better outcomes. This sounds like a huge and very costly effort (at this time), but again the challenges and complexity of cancer are so enormous, that such a task would demand a high degree of collaboration (partnerships?) and coordination. A multiple-front approach was recently aired by CBS 60 Minutes (Dec 07, 2014) – worth watching:
    http://www.cbsnews.com/news/billionaire-doctor-fights-cancer-in-unconventional-way/
    And “Overtime”, where Dr Soon-Shiong boasts of an astounding outcome, “We now have patients with pancreatic cancer that are free of metastasis for five years…”:
    http://www.cbsnews.com/news/the-billionaire-shaking-up-the-world-of-cancer/
    Many hopes are raised for patients and the public. The big question is: Does it work? If so, how soon can it be implemented for so many patients who are racing with time? Can other centers help with this?

  2. gpawelski says:

    There is a lot of cell function (phenotypic) analysis in Dr. Soon-Shiong’s thinking. Cancer is not what people think: cells growing. Cancer is actually the inability of the cells to die. The key is figuring out the genetic mutation that prevents cells from dying a natural death and provide patients with the synergistic combinations of agents to do the job. It’s the agnostic controlled, randomized trialist attitude (show me the money, show me the data) that needs to be overcome before this can be a reality. Whatever clinical response that has resulted to the average number of patients in a randomized trial is no indication of what will happen to an individual at any particular time.

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