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Medical News & Perspectives |

Surgeon, Scientist, and Entrepreneur: One Man’s Fight Against Cancer FREE ONLINE FIRST

Aria Razmaria, MD, MSc
JAMA. Published online September 07, 2016. doi:10.1001/jama.2016.9304
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Nearly a half-century after the US government declared war on cancer, President Barack Obama fired a new salvo during his last State of the Union address. He announced the National Cancer Moonshot Initiative to accelerate cancer research with the ambitious goal of discovering a cure by 2020. At the initiative’s helm is Vice President Joe Biden, for whom the battle became personal last year after losing his son, Beau, to brain cancer.

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Patrick Soon-Shiong, MD

NantWorks

Although the federal plan targeting cancer is new, its name is not. The Cancer Moon Shots program at the University of Texas MD Anderson Cancer Center launched in 2012. And just as Obama announced the federal plan, biotech billionaire and scientist Patrick Soon-Shiong, MD, unveiled his own Cancer MoonShot 2020 program (Lowy D et al. Nat Biotechnol. 2016;34[6]:596-599; http://bit.ly/29vYTnq). Soon-Shiong had discussed his plans with the vice president before Obama’s announcement and now serves on the blue ribbon panel that advises the National Cancer Moonshot Initiative.

An accomplished yet polarizing figure, Soon-Shiong is a board-certified surgeon, adjunct professor at the University of California, Los Angeles (UCLA), physician-scientist, and successful businessman (http://bit.ly/292yRW1). Born in South Africa to Chinese immigrant parents, he received his medical degree from the University of Witwatersrand in Johannesburg. His career took him to Canada and the United States, where he trained under renowned cancer surgeon and researcher Donald Morton, MD, at UCLA. Soon-Shiong’s academic accomplishments include the world's first encapsulated human-to-human islet cell transplant in 1993 for treating type 1 diabetes.

Soon-Shiong left his academic surgical career to follow his passion: developing effective cancer therapies with a focus on immunotherapy. He founded the biopharmaceutical company Abraxis BioScience, which developed the drug Abraxane, a protein nanoparticle delivery technology approved by the US Food and Drug Administration (FDA) for treating metastatic breast, lung, and advanced pancreatic cancer. He sold Abraxis to the Celgene Corporation in 2010 and founded the cancer immunotherapy research company NantKwest. He also chairs the Chan Soon-Shiong Family Foundation.

Recently, Soon-Shiong spoke with JAMA about the National Cancer Moonshot Initiative and his own Cancer MoonShot 2020 program as well as some promising approaches in cancer therapy. The following is an edited version of the interview.

JAMA:You are considered by many one of the driving forces behind the national cancer moonshot initiative, which the president announced this year. How did you become involved?

Dr Soon-Shiong:In July 2015 I invited [former] President Clinton to a summit we held in Jackson Hole [Wyoming] to initiate a conversation to bring together pharmaceutical CEOs [Chief Executive Officers], the FDA, and philanthropy to start what I consider the cancer moonshot. Around that time, I [spoke with] Vice President Biden about his son. In October, I met with him to present a white paper that I called the cancer moonshot. He [later] flew to Los Angeles in November and spent 4 to 5 hours at our [NantWorks] campus and learned in great detail our work on the natural killer cell, dendritic cells, and the vaccine [we’re working on] and asked what else he could do to help us. I said the only thing is to bring together the FDA, the National Cancer Institute, the [pharmaceutical industry], and the academic community to collaborate, and he kindly offered to host us in December at the Naval Observatory Office and in his home.
We had a 5-hour meeting, and the most important thing that came out of it was that the FDA agreed with pharma [representatives] that they should all collaborate and allow novel drugs to be combined. On January 12, President Obama at the State of the Union Address announced that Vice President Biden would be head of “Mission Control,” and the national moonshot initiative was formed.

JAMA:Curing cancer has been a long-standing goal. What advances in the last 20 years and tools available today make it more feasible now to accomplish this goal?

Dr Soon-Shiong:There are two issues. The first question is why haven't we cured cancer. I think the reason we haven't is because we were treating cancer based on wrong assumptions. The first assumption we had was that cancer was based on a single clone, and there was some mathematical analysis that there was linear growth, and if we, therefore, gave chemotherapy in maximum tolerated doses, we would kill the cancer cell and hopefully not kill the patient.
Well, what happened was we killed the cancer cell, but what we didn't realize is that cancer is not a single clone [but] multiple heterogeneous clones. And what we were doing, frankly, with the maximum-tolerated dose chemotherapy, [was] killing the immune system, and releasing and super-selecting the resistance clones, and inducing metastasis.
All of that has now changed because of new insights that cancer is a multiclonal disease and we have the capability to measure protein biomarkers at the quantitative level from the cellular tissue of the patient and know before treatment begins whether the patient has a resistance or chemo-sensitive biomarker. And the technology of supercomputing allows us to take very complex information and bioinformatically find the protein that's secreted by the cancer, and most excitingly, gives us the opportunity to find the abnormal sequence in the cancer cell that is unique to that patient.

JAMA:One focus point of the cancer moonshot initiatives is immunotherapy, with cancer vaccines being 1 research avenue. How far are we from having effective cancer vaccines available?

Dr Soon-Shiong:I truly believe that 2020 is not an insurmountable goal in which we would have an effective vaccine available for cancer. There are 3 ways of getting a vaccine. One is to activate natural killer cells, which would allow the body itself to create the antibodies; another is to create the opportunity to give the patient a specific antibody that allows the patient to induce his or her own vaccine; and the third is to exogenously develop a vaccine through a vector. The vector that I'm most excited about is an adenovirus, where we can transfect the vector with the sequence that is specific to that patient's cancer and re-educate the dendritic cell and induce memory cells. All of these modalities are within reach, in fact, many are in clinical trials.

JAMA:One success in your career has been the development of the cancer drug Abraxane, which holds promise in treating highly aggressive metastatic pancreatic cancer. How commonly do physicians in the United States and around the world use this treatment?

Dr Soon-Shiong:It's slowly becoming the standard of care for metastatic pancreatic cancer both here and around the world, but I'm not satisfied, and the reason is that when I developed Abraxane, I really did not want it to be used at the maximum tolerated dose. How I wanted Abraxane to be used was in low-dose chemotherapy. The goal would be to preserve the immune system while at the same time inhibiting the suppressor cells [with checkpoint inhibitors]. A combination of protocols of standard chemotherapy agents, used correctly and in the appropriate sequence, could actually act as what I call immuno-modulators rather than cytotoxic agents, and that's what we are working toward now.

JAMA:Another area of your research and business focus is the cancer GPS program. Could you give us some insight into this endeavor?

Dr Soon-Shiong:The way drugs work is not at the gene level necessarily but downstream at the protein level. So there was a great need to actually create a test that covers this whole spectrum. A test that measures the entire genome [of the tumor sample] and compare that to the normal sample so that you can find the sequences that [are] different from the patient's normal gene sequence. Then you need to test which [mutations] actually express [protein] downstream. Then if you do find that, you can [perform] what we call targeted proteomics and use a method of mass spectrometry and measure the protein levels in a quantitative way.

JAMA:During your keynote speech recently at the American Urological Association annual meeting in San Diego, you mentioned the urgent call for different specialties to merge forces and fight cancer. How will your cancer moonshot initiative foster this collaboration?

Dr Soon-Shiong:What we are doing in Cancer Moonshot 2020 is creating an infrastructural support for the nation. For example, the amount of data storage that is needed is going to be enormous. The infrastructural need to move terabytes of data, there's no system that's been built. So that's why I took on the National LamdaRail many years ago [that] built 300 000 fiber miles, which can move data around this nation. One of the things we're going to do is support any institution that wants access to a super computer even behind their own firewalls.
The other thing we're going to do with Cancer Moonshot 2020 is bring together a multitude of compounds and molecules that are in phase I, II, and III, and make them fully available to all that want to participate. The third thing we're going to do is make the results openly available [by creating] a portal so that people can communicate. Finally, and probably most important, is the crowd sourcing of intellect, where people share not only information but their expertise so that the patients ultimately could be the major beneficiaries.

JAMA:In your pursuit of the cancer moonshot project, is it more the physician Patrick Soon-Shiong or the businessman Patrick Soon-Shiong who is the driving force?

Dr Soon-Shiong:I don't even see myself as a businessman. I see myself as a surgeon and a physician and a scientist pursuing a dream, and the dream is to use your own biology to treat yourself. I honestly believe you have sufficient cells, be it stem cells or immune cells, in your body to protect yourself. You've been given this as a gift when you were born and my job as a physician is to find a way so that every patient, every doctor, can understand that this opportunity exists. It needs money, however. So whether through philanthropy, business, or government, we all need to contribute to make this happen.
In addition, I'm most interested in making sure that this kind of technology is not only limited to the rich. I was born in South Africa and grew up in apartheid. I understand how the black community suffered, and we need to make sure that whether you're rich or poor, these opportunities exist. Whether that's considered a business or not, I don't know. All I know is that we are here to help people and patients.

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Patrick Soon-Shiong, MD

NantWorks

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