As reported today at the American Society of Clinical Oncology (ASCO) meeting, researchers at the Nagourney Cancer Institute and Metabolomycs, California-based biotechnology companies working with the FibroFighters Foundation, combined mass spectrometry with functional profiling in Fibrolamellar cancers to identify previously unrecognized therapeutic vulnerabilities in this highly lethal childhood malignancy. The investigators showed that Fibrolamellar cancers appear to arise through changes in cellular metabolism.
Fibrolamellar cancer is a rare form of liver cancer that afflicts young adults between 15 and 25 years of age. Surgical resection is the principal form of therapy with chemotherapy used post operatively and for patients with advanced or recurrent disease. When Fibrolamellar cancers were examined by Ex vivo analysis of programmed cell death (EVA/PCD), a functional profiling laboratory technique pioneered by the Nagourney Cancer Institute that measures how tumors respond to drugs, results showed resistance to standard drugs but unexpected sensitivity to inhibitors of cellular metabolism. When they then examined the blood of Fibrolamellar patients by mass spectrometry “the metabolic signatures stood out like a sore thumb compared to normal controls,” said Dr Robert Nagourney, senior investigator on the study.
This could explain why Fibrolamellar cancers have proven so resistant to conventional chemotherapy, yet appear sensitive to drugs that target metabolic pathways associated with nutrient uptake and utilization.
With only 600 new cases in the US each year, Fibrolamellar cancers have been difficult to study, but the disease is known to carry a DNA gene-rearrangement (DNAjB1-PRKACA) that appears to change cellular metabolism. The results of the functional profiling analyses combined with mass spectrometry confirm metabolic vulnerabilities that can be exploited therapeutically.
“For over a century, scientists have been trying to connect cancer to cellular energy production and metabolism. But it wasn’t until the development of quantitative mass spectrometry that we could test many of these hypotheses,” said Nagourney. Complete results are published in the current issue of the journal Cancers.
Metabolomics is a new field of science that uses mass spectrometry to measure the quantity of metabolic byproducts in blood and other body fluids. While mass spectrometry has been used in many disciplines, the advent of “targeted” mass spectrometry has now provided direct clinical applications.
Ex Vivo Analysis of Programmed Cell Death (EVA/PCD) is a laboratory platform that measures the efficacy of drugs and combinations, using each patient’s tumor tissue to select the most effective therapy before they’re administered to patients, providing significantly improved response and survival.
FibroFighters is a non-profit foundation dedicated to the study and treatment of Fibrolamellar cancers. It was founded by Tom Stockwell, who lost his own son to the disease at the age of 22. Working with Dr Paul Kent, pediatric oncologist and FibroFighters medical director, Stockwell has made it his mission to advance the field.
The work was made possible due to the generous support of the Bickerstaff Family Foundation, The Vanguard Cancer Foundation, The Rosalie and Harold Rae Brown Foundation and the Nagourney Cancer Institute.
The Nagourney Cancer Institute is a Long Beach-based cancer research institute that developed the EVA/PCD functional profiling platform offering patients with advanced and recurrent cancers significantly improved response and survival.
Metabolomycs Inc. is a Long Beach, California-based biotechnology company that has pioneered the application of targeted mass spectrometry in cancer diagnostics and prognostics.
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