Dr. Yibin Deng leads team with new work published in ‘EBioMedicine’
Findings from recent preclinical studies at The Hormel Institute may offer new therapeutic strategies for treating aggressive, lethal forms of prostate cancer.
Dr. Yibin Deng, leader of the “Cell Death & Cancer Genetics” research section at The Hormel Institute, and his team were recently published in the open-access journal EBioMedicine. Their studies found that by co-targeting hexokinase 2 (HK2)-mediated aerobic glycolysis with 2-deoxyglucose (2-DG) and ULK1-dependent autophagy with chloroquine (CQ) tumor growth is suppressed.
The research section’s past studies identified HK2 – an enzyme that catalyzes the first committed step in glucose metabolism – as a potential therapeutic target for prostate cancer patients who carry PTEN and TP53 gene mutations.
HK2 is upregulated in prostate cancer cells that have Pten/p53 gene mutations, and it is required for Pten/p53-deficiency driven prostate tumor growth, Deng said.
The team’s recent findings show that targeting HK2 along with ULK1-dependent autophagy (physiological process that deals with destruction of cells in the body) suppresses tumor growth.
By pharmacologically targeting HK2 with 2-DG, the normal occurrence of cell death, known as apoptosis, is inhibited due to 2-DG simultaneously being prone to aiding ULK1-driven autophagy and therefore has tendencies to maintain cell survival. The team thus targeted HK2 with 2-DG and ULK1 with CQ to destroy the cancer cells.
“Our studies in the preclinical models provide a novel and efficacious therapeutic strategy for the subsets of currently incurable castration-resistant prostate cancer (CRPC) patients carrying PTEN and TP53 mutations,” Deng said. “I look forward to collaborating with clinicians to translate our bench work to clinical trials.”
Prostate cancer is the second-leading cause of cancer-related deaths in men after lung cancer in the United States.
The Hormel Institute team collaborated on the project with researchers from Penn State College of Medicine in Hershey, Pennsylvania. The article can be found online at http://dx.doi.org/10.1016/j.ebiom.2016.03.022.
EBioMedicine is a journal supported by CellPress and THE LANCET that accelerates useful research by bridging the entire continuum between basic biomedical and clinical research.