Researchers at UCLA's Jonsson Comprehensive Center used a strategy that tracked cancer cell consumption of nucleosides to identify a group of liposarcoma tumors that are visible to a type of positron emission tomography (PET) imaging and sensitive to chemotherapy.
Liposarcoma, the most common type of sarcoma, is an often deadly form of cancer that develops in fat cells. These tumors are not consistently visible using FDG PET scanning, but scientists led by Heather Christofk, assistant professor of molecular and medical pharmacology at UCLA's Jonsson Comprehensive Cancer Center, used a metabolomic strategy that detected nucleoside salvage activity in tumor cells taken from patient samples, grown in the laboratory, and grown in mouse models. That nucleoside activity was visible by PET scanning with a tracer substance called FAC (FAC PET).
In the study, published online ahead of print in Cancer Discovery, the research team also found that liposarcoma cells with high nucleoside salvage activity are sensitive to the standard chemotherapy drug gemcitabine. Thus, in clinical practice this strategy might be used to identify, at diagnosis of liposarcoma, a group of patients who would respond well to gemcitabine chemotherapy, saving time on other treatments and possibly extending the lives of this sub-group of liposarcoma patients.
"It was a satisfying study because it has translational potential for liposarcoma patients now, and this is a deadly disease," said Christofk, "our metabolomic strategy is also generalizable to treatment strategies for other cancers, and that is something we hope to do."
This study was a collaboration between basic scientists and clinicians, following the translational paradigm of bench to bedside discoveries. "This was an outstanding transdisciplinary project between a diverse group of physician scientists and basic scientists that translates molecular oncology from the laboratory to the clinic in a rapid and clinically relevant manner," said Dr. Fritz Eilber, associate professor of surgery and molecular and medical pharmacology and an investigator on the study, "the findings from this work can be used to directly impact the care of patients with this morbid and lethal malignancy."
This research was supported in part by NIH grant P50CA0863062. Christofk is a Damon Runyon-Rachleff Innovation awardee supported in part by the Damon Runyon Cancer Research Foundation, the Searle Scholars Program, the NIH Director's New Innovator Award (DP2 OD008454-01), and the Caltech/UCLA Nanosystems Biology Cancer Center (NCI U54 CA151819).
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2012, the Jonsson Cancer Center was once again named among the nation's top 10 cancer centers by U.S. News & World Report, a ranking it has held for 12 of the last 13 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.