The Billionaire Cancer Researcher

The Billionaire Cancer Researcher

L. Michael Glode, MD, FACP, FASCO

Dec 17, 2014

Several patients/friends recently told me about the 60 Minutes piece highlighting the ongoing efforts of Patrick Soon-Shiong, a surgeon who was involved in the development of protein-bound paclitaxel (Abraxane™) and has become worth $11B as a result. So, I did my duty and watched the segment on the Internet.

Let it first be said that the optimism in this video is compelling, and for the most part based on science that has been going on for the past decade or so in labs all over the country. The 60 Minutes team working with Dr. Soon-Shiong highlighted in a visually compelling, and mostly understandable way, the progress that is being made using the latest technology and understanding of cancer biology. I will highlight this as follows:

  1. Massive computer technology and sequencing advances allow “all” of the mutations that characterize a cancer cell to be displayed.
  2. Drug development to attack vulnerable biologic pathways within cancer cells is accelerating. 
  3. The possibility of finding the gene mutations driving these cells by looking at circulating tumor cells portends a (mostly) promising way of sampling what is going on within a patient, yet not having to biopsy the tumors.
  4. The recent breakthroughs in enhancing immune responses to tumors by shutting down the innate immune checkpoint controls appear to offer great promise for “wiping out” residual/resistant tumor cells.

With that summary, let me urge anyone who watches/watched the video to pay close attention to my good friend, Derek Raghavan’s commentary in the segment. Derek is one of the most insightful and honest translational medical scientists I know. In essence, he points out that although Dr. Soon-Shiong is applying an “all of the above” approach to the attack on cancer, there will still be enormous amounts of work to be done and, thereby, hints at the problem I have with the video—overselling hype/hope is a specialty of the media.

Presenting the single patient with pancreatic cancer who is doing well is an example of this focus on the “sizzle and not the steak” approach. I take nothing away from what a billion dollars can do to pull the existing technologies together and applaud Dr. Soon-Shiong’s efforts. As a matter of fact, one of the techniques he touches on, using low, continuous doses of chemotherapy, is something we may have been the first to try in prostate cancer several years ago and published here.

So, what are the cautionary issues?

1. The sheer number of mutations found in most cancers (and perhaps especially in prostate cancer where the term “shredding of the genome” has been used) make attacking all of the pathways at once nearly impossible. If even one cell can further mutate in the face of having, say six or seven drugs being given to shut down the mutations, it will survive to become the dominant and lethal metastatic problem. This is layered onto the challenge of using “all six drugs” together, which will more than likely compound the toxicities to the host when compared to using one of them at the optimal dose.

2. Tumor heterogeneity. In an incredible tour-de-force, a team of scientists at the Cancer Research UK London Research Institute did whole genome analysis of the original kidney cancer in four patients, as well as in their metastases. The graphic of how the research was done is shown here:

Each spot in the original tumor, as well as each metastasis, had a somewhat unique set of mutations. Thus “personalized medicine,” the favorite buzzword of the moment in medicine, has a huge challenge in cancer, since there might be different combinations of drugs required for each metastatic site in some patients. The same might apply even for the evaluation of individual circulating tumor cells, of course, which is now possible. A cell coming into the research syringe at one time might reflect a tumor deposit in one area, while the next cell isolated could be coming from somewhere else. 

3. The excitement over using the most clever of the immune approaches, including the checkpoint inhibitors and the CART cell approach havesignificant challenges, either because of unleashing autoimmunity, or the very high costs of manipulating each individual patient’s T-cells in order to come up with the autologous cancer-fighting cell treatment.

So, here’s to the optimism and billionaire strategies, and we all hope it moves forward quickly and successfully. And here’s to 60 Minutes for highlighting the amazing biology and progress that is being made.

Hope is one of the keystones of human progress, whether it is landing on Mars or repairing a broken relationship. Love and hope are what make life worth living. May your holiday celebrations be filled with both!

This post originally was published on prost8blog, a blog to help patients and their families understand various aspects of prostate cancer, and is reprinted with permission of Dr. Glodé.

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Comments

Michael A. Thompson, MD, PhD

Dec, 18 2014 4:28 PM

Great post!

Happy Holidays,

Mike 

Frederick E. Millard, MD

Feb, 02 2015 2:25 PM

Mike, I'm a little late in seeing this, but thank you so much for adding your respected voice to the necessary counternarrative to pie in the sky.  We will make progress, and it will be helped by genomic advances, but it will come from painstaking and thoughtful work as it always has, not from hype and publicity. 

fred  


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