A team of Terry Fox-funded researchers has revealed that genetic alterations affecting the metabolic pathways of cancer cells drive outcomes in patients diagnosed with pancreatic cancer.
The findings, published in Clinical Cancer Research (Sept. 2019), provide a new way to subtype pancreatic cancers which, in turn, may help personalize treatments for patients diagnosed with this deadly disease.
“The lack of clinically actionable prognostic biomarkers that stratify pancreatic cancer patients is a historic gap in pancreatic cancer research,” says Dr. David Schaeffer, a gastrointestinal pathologist, co-director of the Pancreas Centre BC, and a co-lead investigator for TFRI’s Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC) project. “This finding provides a new avenue to search for these biomarkers while also identifying potential targets that could be explored for the creation of new cancer treatments.”
At nine per cent, pancreatic cancer has the lowest five-year survival rate of any major solid cancer. It has few known symptoms, limited treatment options and no clinically relevant biomarkers that allow doctors to individualize care for patients.
To fill this gap, the team analyzed genomics data from a cohort of 325 patients with pancreatic ductal adenocarcinoma (PDAC) focusing on two specific metabolic pathways that have been implicated in tumour biology: glycolysis and cholesterol metabolism. This analysis allowed them to group pancreatic cancers into four unique metabolic classes which corresponded to survival differences. A glycolytic gene profile associated with the shortest survival was linked to a known aggressive pancreatic cancer subtype. Patients with tumours with an increased cholesterol synthesis profile had longer time to recurrence and better outcome. The findings suggest that targeting distinct metabolic vulnerabilities of pancreatic tumours may be a new strategy for the development of individually tailored cancer treatments in order to inhibit tumour growth, render tumours less aggressive or more susceptible to therapy.
According to Dr. Schaeffer, being able to determine how patients will fare when exposed to current treatments is necessary to begin personalizing treatments in ways that improve survival and reduce negative side effects associated with current therapies.
“I have this big vision that in five years we will be able to take a biopsy of a patient before they begin treatment, subtype it and tell the treating physician and the patient that given the unique characteristics of their cancer, this is the best treatment option for them to follow,” says Dr. Schaeffer. “We still have a long way to go before we can do that, but this paper is an important piece in the overall puzzle of understanding subtypes of this disease and moves us one step closer to that point.”
Altered Gene Expression along the Glycolysis–Cholesterol Synthesis Axis Is Associated with Outcome in Pancreatic Cancer
Joanna M. Karasinska, James T. Topham, Steve Kalloger, Gun-Ho Jang, Robert E. Denroche, Luka Culibrk, Laura M. Williamson, Hui-Li Wong, Michael KC Lee, Grainne M. O'Kane, Richard A. Moore, Andrew J. Mungall, Malcolm J. Moore, Cassia Warren, Andrew Metcalfe, Faiyaz Notta, Jennifer J. Knox, Steven Gallinger, Janessa J. Laskin, Marco A. Marra, Steven J.M. Jones, Daniel J. Renouf and David F. Schaeffer
The study was partially funded by a Terry Fox Translational Research Program grant to Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC)