The Emperor of All Maladies’ New Clothes

Ken Burn’s series “The Emperor of All Maladies” from Siddhartha Mukherjee’s book of the same title ppbs logorovides an interesting and informative historical perspective on mankind’s efforts to confront cancer as a disease.

Beginning with ancient references to human malignancy, the series goes on to explore radical surgery and the earliest use of radiation but really gains traction in the mid-20th century with the discovery of the first chemotherapy drugs. While the nitrogen mustard derivatives were being studied under a veil of military secrecy, Dr. Sidney Farber in Boston explored the B-vitamin analogue, aminopterin, for the treatment of childhood leukemia. (You can read more about this in my book Outliving Cancer.)

Through the ensuing decades, seemingly stunning victories ultimately fell in crushing defeats, while the promise of single agents, then multi-drug combinations, followed by dose-intensive therapies, and finally bone marrow transplantation yielded few cures but delivered ever increasing toxicities. Clifton Leaf, a cancer survivor himself who created a stir with his controversial 2003 Fortune Magazine article entitled “Why We Are Losing the War on Cancer and How to Win It” described his own disappointment with the slow pace of progress.

Screen shot Emperor of All MaladiesThe last episode examined our growing understanding of human genomics and segued by interviews with Richard Klausner, former director of the National Cancer Institute; and Harold Varmus, the current NCI director; to Michael Bishop, Eric Lander and Francis Collins who luxuriated in the clinical potential of human genomics and the coming era of big science.

The final part was an interview with Steven Rosenberg, one of the earliest pioneers in immunotherapy and Carl June whose groundbreaking work with chimeric antigen receptor T-cells is among the most recent applications of this important field.

The take-home message would seem to be that despite the fits and starts we are now at the dawn of a new age of big science, big data and genomic breakthroughs. What was missing however was an examination of where we had gone wrong. It would seem that the third rail for this community is an honest assessment of how a small coterie of investigators who championed only certain ways of thinking over all others commandeered all the money, grants, publications, chairmanships and public attention, while patients were left to confront a disease from which survival has changed very little, at ever increasing costs and toxicities.

Another thing that came through was the very human side of cancer as a disease and the kindness and emotional support that family members and parents provided to those afflicted. I couldn’t help but feel that these individuals had been cheated: cheated of the lives of their family members, cheated of the resources that could have pursued other options and cheated of the well-being that these poisonous and dose-intensive regimens rained upon them in their last days.

As science has become the new religion and scientists the new gurus, one message that resonated was that many of these gurus were false prophets. They are too self-absorbed to question their own dogmatic belief systems in dose-intensity or multi-agent combinations, all of which fell painfully by the way side as the next therapeutic fad emerged. Will our current love affair with the gene prove to be little more than the most current example of self-congratulatory science conducted in the echo chamber of modern academia?

Victories against cancer will be won incrementally. Each patient must be addressed as an individual, unique in their biology and unique in their response probability. No gene profile, heat map, DNA sequence or transcriptomic profile has answered the questions that every patient asks; “What treatment is best for me?” Dr. Mukherjee himself used the analogy of the blind men and the elephant. Unfortunately, there was little discussion of how much that parable may apply to our current scientific paradigms.

It is time for patients to demand better and refuse to participate in cookie-cutter protocols.
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Physicians should become more familiar with the fundamentals of physiology and biochemistry to better understand the principles of cancer prevention at the level of diet and lifestyle.

Finally, while we wait with bated breath, for the arrival of glorious gene profiles widely touted as the future answer to all of cancer’s most vexing questions, patients should throw off the yoke of one-size-fits-all approaches and demand laboratory platforms, such as the EVA-PCD assay, that are available today to make better use of existing treatments.

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 The Emperor of All Maladies’ New Clothes

  1. Now cancer is big problem of people, cure for cancer like a global war. Huh….i found video The Emperor of All Maladies here:
    http://theemperorofallmaladies.net/2015/04/13/cancer-the-emperor-of-all-maladies-magic-bullets/

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