null $2 million USD to investigate new approaches for prostate cancer treatment
RI-MUHC researcher David P. Labbé and a team of international collaborators will investigate the mechanisms and components of precision nutrition to improve treatment options for lethal prostate cancer
Despite new drugs and advances in research, the metastatic, castration-resistant form of prostate cancer known as CRPC has no cure, and it is likely to kill 360,000 men worldwide this year.
A new grant of $2 million USD was announced in October by the Peer Reviewed Medical Research Program (PRMRP) of the U.S. Department of Defense. These funds were awarded to David P. Labbé, PhD, a scientist at the Research Institute of the McGill University Health Centre (RI-MUHC), who will lead a team of international collaborators. A researcher in the Cancer Research Program at the RI-MUHC, Labbé has spent his career studying the molecular biology of prostate cancer, in particular the impact of diet on molecular events related to tumour progression. This award will fund research to improve outcomes for patients impacted by this devastating diagnosis.
With co-principal investigator Eva Corey, PhD, an expert in patient-derived models of prostate cancer from the University of Washington, and collaborators from the United States, Australia and Canada, Labbé and his team will conduct state-of-the-art preclinical trials that aim to understand the effect of precision nutrition on castration-resistant prostate cancer, or CRPC.
The new proposal builds on earlier work by Labbé and others, which has shown that saturated fat intake fuels prostate cancer progression and led to their recent development of a nutrition-based strategy designed to potentiate current prostate cancer therapies. This promising approach could prevent or reduce the impact of disease progression.
“For example, there are some recently approved human treatments using drugs known as PARP inhibitors that are clinically used but potentially effective in only around 13 to 20 per cent of patients with metastatic CRPC,” says Labbé. PARP, or poly-ADP ribose polymerase, is a protein that helps damaged cells to repair themselves, while PARP inhibitors can help prevent that repair work in cancer cells. “Similarly,” Labbé notes, “other DNA-damaging therapies such as radiotherapy or prostate-specific membrane antigen radionuclide therapy are not effective in all patients.”
The new and provocative approach of this study is to focus on maximizing the efficacy of DNA-damaging therapies using precision nutrition. The researchers aim to identify elements central to diet-dependent deregulation of the DNA damage response (DDR), and to define dietary signatures of aberrant activation of the DDR or response to DNA-damaging therapies in patients.
“There are really four fundamental questions we want to answer,” explains Labbé. “First, what is the optimal strategy for using precision nutrition for tumour sensitization? We also aim to determine the diet-related elements that are central to deregulation of the DDR, as well as which elements of the DDR machinery are critical for the precision nutrition-mediated tumour sensitization. Finally, we hope to learn if a specific dietary regimen or dietary signature – identified, that is, from the blood of a patient – can predict deregulation of the DDR and the response to DNA damaging therapies.”
The researchers’ ultimate goal is to translate their work into human clinical trials and improve survival of prostate cancer patients. Adds Labbé, “Our groundbreaking approach raises the exciting near-term possibility of a novel precision nutrition approach to potential cancer treatments for metastatic, lethal prostate cancer.”
About the grant
Precision nutrition increases efficacy of DNA-damaging therapies in prostate cancer
$2,000,000 (USD), Operating Grant
Department of Defense; Peer Reviewed Medical Research Program (PRMRP) Investigator-Initiated Research Award – Partnering PI Option
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Diet-Dependent Metabolic Regulation of DNA Double-Strand Break Repair in Cancer: More Choices on the Menu
December 12, 2022