Grant for Human Trials of Cancer Treatment
Based on Longo’s breakthrough research published last March in PNAS Early Edition, which found that fasting for two days protected healthy cells against chemotherapy in both mice and human cells in test tubes, the highly anticipated experimental method will be tested on cancer patients beginning in early November.
Longo, associate professor at the USC Davis School of Gerontology and USC College, discovered that mice given a high dose of chemotherapy after 48 hours without food continued to thrive, while the same dose killed half the mice fed normal diets and caused lasting weight and energy loss in the remaining survivors.
In human cells, test tube experiments revealed a greater resistance to chemotherapy for healthy cells after a short period of fasting while cancerous cells were reduced.
“We will test this approach with different carcinomas and chemotherapy drugs in mice and also propose parallel clinical human studies to see for the first time whether short-term fasting can protect patients against the side effects of chemotherapy,” Longo said.
For many years, defending against the debilitating effects of chemo has been a top goal of cancer research with treatment focused primarily upon cancerous cells. Longo’s method proposes a joint attack that targets both cancerous cells and protects healthy cells.
“Protecting all healthy cells at once is the primary focus in the anti-aging field,” Longo said.
If it is effective, the chemotherapy shield would allow oncologists to potentially control cancers, making chemotherapy less toxic to the rest of the body.
“Proposed studies have the potential to provide data that could have a broad impact on cancer treatment worldwide and across tumor types in the near future,” Longo said. “The resulting data will also serve as an impetus for the development of drugs that mimic the effects of fasting.”
Starved cells go into survival mode, Longo said, characterized by extreme resistance to stresses. In essence, these healthy cells are waiting out the lean period, much like hibernating animals. But tumors respond differently to starvation; they do not stop growing, nor do they hibernate because their genetic pathways are stuck in an “on” mode.
Longo realized that the starvation response might differentiate normal and cancer cells by their increased stress resistance and that healthy cells might withstand much more chemotherapy than cancer cells.
“This could have applicability in maybe a majority of patients,” said Quinn, practicing oncologist and medical director of USC Norris Hospital and Clinics.
Cancers of the bladder and lung will be tested first.
The initial stage of the trial will determine safety and feasibility of fasting. Researchers will first examine whether a 24-hour fast is safe. If so, they will test a 48-hour fast, and on up to 72 hours if it is deemed feasible.
“The second stage of the trial will randomly assign patients to eat normally before chemo or to fast for the amount of time we select based on the experience in the first stage,” said Tanya Dorff, assistant professor of clinical medicine at USC Norris Cancer Center and co-principal investigator of the study.
Given three years of funding for trials, comprehensive results should become available much earlier.
“We will certainly see results within two years, allowing time to accrue cohorts in both stages of the trial, and may have an earlier glimpse if enrollment is rapid,” Dorff said.
The plan is not to give higher than standard doses of chemotherapy to cancer patients, rather patients will get the same treatment as if they did not participate in the clinical trial, Dorff said.
“The goal is to see a reduction in the frequent toxicities that we currently see with this standard regimen – instead of 71 percent having grade three or four neutropenia (low white blood cells) – we are hoping to see only 36 percent experience it. Instead of 57 percent grade three or four thrombocytopenia (low blood platelets), we are hoping to see 29 percent, etc. All standard chemo side effects will be assessed in fasting patients and controls to look for a difference.”
The potential to make an immediate difference is what attracted the attention of the V Foundation for Cancer Research, which began as the dream of Jim Valvano, the former North Carolina State basketball coach and award-winning broadcaster, who died of cancer in 1993.
Over the past 14 years, the organization has raised more than $70 million and awarded cancer research grants in 37 states and the District of Columbia.
“The scientific advisory board of The V Foundation selects the most promising researchers to make advances in cancer research,” said Nick Valvano, CEO of The V Foundation.
Grants such as the one won by Longo and Quinn in translational clinical research facilitate the evolution of projects from the laboratory to the clinic.
“Dr. Longo shows interesting potential with his research on the effects of fasting to protect healthy cells from toxicity,” Valvano said. “This novel approach may ease the effects of chemotherapy and make patients more comfortable through the treatment process.”
Amy Lee, professor of biochemistry and molecular biology at the Keck School of Medicine of USC, is also a co-principal investigator.
Carl Marziali contributed to this article.
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USC in the News
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The Chronicle of Higher Education mentioned USC’s $6 billion fundraising campaign. The story noted that USC had already raised $1 billion in a “quiet phase,” including the $200 million naming gift from USC Trustee and alumnus David Dornsife and wife Dana Dornsife to the USC Dornsife College.
The Guardian (U.K.) highlighted two major gifts to USC in a list of the 10 biggest philanthropic benefactors in America. The list included the $200 million naming gift from USC Trustee and alumnus David Dornsife and wife Dana Dornsife to the USC Dornsife College, and the $110 million gift from USC Trustee and USC Viterbi School alumnus John Mork and wife Julie to create the USC Mork Family Scholars Program.
The New York Times featured the USC U.S.-China Institute documentary “Assignment: China — The Week that Changed the World.” The documentary, part of a series, examines media coverage of the 1972 Nixon trip that reshaped U.S.-China relations after a quarter century of isolation and hostility. “People look back now and take it for granted that the outcome was preordained,” said the institute’s Mike Chinoy, who produced the documentary. Voice of America also featured the story.
Los Angeles Times featured the Oscar Senti-meter, a tool developed by the USC Annenberg School, Los Angeles Times and IBM that analyzes thousands of tweets about the Academy Awards nominees. The story noted that Mexican actor Demian Bechir received an enormous boost on Twitter the day of the nominations, with a total of 6,893 tweets mentioning him, a 47-fold increase from the day before. The story noted the tool uses language-recognition technology developed in collaboration with USC Viterbi School’s Signal Analysis and Interpretation Lab.
The Times of India (India) featured a three-day medical emergency training workshop organized in association with USC. At the workshop, held at GCS Medical College in India, 50 doctors and more than 100 paramedics learned how to improve emergency support systems. William Mallon of the Keck School of USC said that discussion topics included the use of portable ultrasonic devices to scan patients. “The ultrasound applications help physicians make accurate and timely decisions,” he noted. Daily News & Analysis (India) also featured the workshop.
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