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Health & Science

Frontline Cancer: Innovative science; Friending viral foes

Scott M. Lippman, M.D. is director of UC San Diego Moores Cancer Center.
Scott M. Lippman, M.D. is director of UC San Diego Moores Cancer Center.
(File Photo)

FRONTLINE CANCER:

The spread of coronavirus wasn’t the topic of the 16th annual Industry/Academia Next Generation Precision Oncology Symposium, but it was a fascinating interlude when Scott Gottlieb, M.D., the 23rd Commissioner of the FDA, commented on aspects of the public health crisis while in town Feb. 20 to accept the Duane Roth Achievement Award.

While most coronaviruses cause common cold, three have become more dangerous, crossing species to people: the first was SARS CoV in 2003 and the latest to “make the jump” — SARS-CoV-2, the virus which causes “Coronavirus Disease 2019” or COVID-19. According to Dr. Gottlieb, there was a large, late-season spike in U.S. “flu-like” illness, raising the unsettling possibility that the novel corona virus may have been here earlier than initially thought.

Talking about COVID-19 during this symposium was just another indication of his impressive insight and leadership. He clearly saw what was coming when he called for a more rapid screening program, akin to his initiatives while he was the FDA Commissioner — encouraging manufacturers to intensify diagnostic test development and availability and to accelerate viral screening at the onset of the Zika virus outbreak — at a time when little was known about the disease.

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He was concerned about the delay in screening for COVID-19 in the United States, resulting from the now well-described CDC test kit flaws and public health laws restricting testing by academia or local labs.

A widely held current view in the public health community is the more screening the better (“test, test, test”) once we have adequate capacity (and the United States is rapidly getting there; 27,000 people tested this day, one week ago) — case counts are expected to quickly rise.

The call for robust social distancing is also indicative of his clear grasp of public health issues and were made before the media “went viral” — Italy went on complete lockdown, World Health Organization (WHO) declared pandemic, Broadway closed, the NCAA Final Four was cancelled, and Gov. Gavin Newsom declared a statewide lockdown — our lives will forever be changed by the acceleration of technologies and innovations like Telehealth, along with a myriad of other “curve-flattening” activities used to meet this challenge to public health.

An “idealist without illusion” were the words Nathan Fletcher, 4th District San Diego County Supervisor, used during the award ceremony to describe the late and beloved San Diegan, Duane Roth, whose innovation and leadership in the biotech industry had tremendous impact well beyond California. The words are equally applicable to Dr. Gottlieb, who didn’t hesitate to confront the emergent viral threat with any less vigor than when he bucked traditional FDA methods of drug approval and took on the e-cigarette industry targeting of nicotine addiction in children.

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Perhaps Dr. Gottlieb’s major legacy in drug development as FDA Commissioner are the processes and frameworks he created. This led to an inflection of pace at the FDA (marking pivotal changes in science and technology, not Agency policy, he added) allowing rapid science-driven clinical development of gene therapies that, interestingly, include virus-based oncolytic agents — a major new class of next generation precision oncology — at the interface of gene therapy and immune oncology.

Frontline Cancer Nathan Fletcher and Scott Gottlieb-cropped-jpg.jpg
4th District San Diego County Supervisor Nathan Fletcher (left) presents Dr. Scott Gottlieb with the Duane Roth Achievement Award and proclaims Feb. 20, 2020 as “Scott Gottlieb Day.”
(Courtesy Photo)

As further recognition of the Commissioner’s transformative leadership, Feb. 20, 2020 was officially declared “Scott Gottlieb Day” in San Diego by Supervisor Fletcher, who specifically highlighted the Commissioner’s leadership in investigating the vaping epidemic and related illnesses.

It was FDA recommendations under Dr. Gottlieb’s tenure that prompted our County Board of Supervisors to ban flavored tobacco/vaping devices until they are regulated and certified by the FDA. It was a bold and prescient law, one week after his Roth Award presentation, the U.S. House of Representatives passed a bill to ban flavored smokeless tobacco products.

New, emerging viruses, like the novel corona virus, are scary for good reason. While not considered true forms of life, viruses have been around for as long as life on Earth; and can produce immune misfiring.

Some viruses can cause cancer. The Nobel Prize-winning discovery of the HPV/cervical cancer link led to breakthrough vaccines (and screening), transforming cancer interception and prevention with vast and increasing global impact — not only cervical neoplasia, but also vaginal, vulvar, penile and anal cancer and the current epidemic of a common class of head and neck cancers in the United States and other developed countries.

While viral epidemics pose severe challenges to society, there are instances where thoughtful efforts can turn these foes into potential friends in the fight against cancer.

Little is known about COVID-19 and cancer other than reported increased mortality in vulnerable populations. COVID-19 effects and response measures in clinical oncology and cancer research have been multifaceted and unprecedented. The National Cancer Institute director and his leadership team held a teleconference (replacing the annual in-person meeting) with NCI Cancer Center directors stressing the critical importance of cancer science to the development and translation of life-impacting interventions, an integral pillar upon which our cancer patients depend; in a remarkable follow-up action, issued an urgent request to NCI-designated Centers to stimulate COVID-related cancer research.

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The requested proposals are to support efforts to investigate SARS-CoV-2 in cancer, including research priorities of clinical trials, natural history and community monitoring/care delivery. In addition to the NCI directors meeting, major conferences were cancelled, from the NCCN (of 28 elected leading U.S. cancer centers, including four in California) which continually monitors and sets standard-of-care guidelines and pathways for patients with all cancer types/subtypes, to the annual American Association for Cancer Research meeting where 22,000 members globally were expected here in April.

Most importantly, cancer-care providers, researchers, trainees and support staff are working intensely overhauling/streamlining clinic operations, without interrupting the life-saving treatments — some only available for patient access at NCI-designated Comprehensive Centers, including breakthrough vaccines, other immune and/or cell-based regenerative therapies.

Understanding the basis of exquisite tissue specificity can help us exploit viral mechanisms acquired through centuries of evolution to treat human cancer. Studies of this natural process have led scientists to exploit viruses to engineer a new class/field of precision therapy to selectively target and kill cancer cells — termed oncolytic viruses.

Zika virus is a case in point. Originally isolated in 1947 from a monkey in the Zika forest of Uganda, and only later skipping species, Zika was initially thought to cause a self-limiting and mild febrile disease.

However, epidemic infection outbreaks in French Polynesia in 2013-2014, as well as Brazil and other Latin American countries in 2015-2016, associated Zika with birth defects, including small heads in babies and other congenital abnormalities as well as paralysis and brain infection.

These terrible complications gave researchers an idea.

Fundamental studies of Zika virus by UC San Diego Moores Cancer Center researcher Jeremy Rich, M.D., led to a remarkable and unexpected discovery — Zika, despite no causative connection to cancer, has profound oncolytic activity, selectively killing brain-tumor (called glioblastoma) stem cells.

Separate reports last month from two groups of UCSD scientists (including Rich) built on these findings — identifying how Zika enters tumor (but not normal) stem cells, and now permits the ability to develop engineered oncolytic viruses, offering an exciting precision immune/gene therapy for this lethal, resistant tumor.

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During a crisis and times of extreme pressure, a community can either come together or fall apart. It is heartening to know that the San Diego community is rallying to fight the COVID-19 outbreak together, and we will come out stronger from this. While there are several, one example of the spirit of community service from UCSD Moores Cancer Center that comes to mind is collection of personal protective equipment for preventing the spread of COVID-19 to and through healthcare workers.

Leveraging the communications processes put in place for our NCI-designated comprehensive cancer center, we put out a call for collection of masks. With leadership from Mitchell Kronenberg, Ph.D., the La Jolla Institute for Immunology team stepped up to answer this call and sent over 90 N95 masks to Moores Cancer Center.

At the national level, Moores and other NCI-designated center members of AACI have come together on AACI’s Slack workspace dedicated to COVID-19 — an example of removing barriers to actively facilitate communication and share information on a real-time basis as this outbreak rapidly unfolds.

Strategic containment is impactful, vaccine and therapeutics development is underway, as is basic research into every aspect of SARS-CoV-2, including classic viral characterization and transmission studies such as surface stability on plastic. In the meantime, technology also offers a way forward and some comfort to California residents on lockdown; this time with home networking and perhaps Netflix to take the sting out of a possible COVID-cation.

No one knows yet what the impact of COVID-19 will be, but as with Zika before, we must follow public health guidelines and mandates until the pace of the novel coronavirus pandemic is better understood, and we get to the other side, push down the steepness of the curve, and drive research that may eventually turn this viral foe into novel cancer therapy.

Scott M. Lippman, M.D. is director of UC San Diego Moores Cancer Center. His column, “Frontline Cancer,” appears periodically in this publication. He can be reached by e-mail: mcc-dir-lippman@ucsd.edu


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