Researchers discover new way to ‘starve’ prostate cancer tumors at the cellular level

New research led by a team of scientists at the Indiana University School of Medicine and their collaborators has discovered a new vulnerability in animal models of prostate cancer that deprives prostate tumors of essential nutrients and delays their growth, which could lead to the development of new treatments against this deadly disease. .

Led by Kirk Staschke, Ph.D., research assistant professor of biochemistry and molecular biology, of the IU School of Medicine, and Ronald C. Wek, Ph.D., Showalter Professor of Biochemistry, the study was recently published in Scientific signage.

Prostate cancer is a leading cause of cancer death among American men. Current treatments target the hormone testosterone, which prostate cancer cells need to grow. Unfortunately, prostate tumors often become resistant to these treatments, leaving doctors with few options to stop the disease.

The research team has discovered a promising new way to target prostate tumors by depriving them of essential nutrients called amino acids. Like other tumors, prostate cancer cells need plenty of nutrients to support their rapid growth. As nutrients become depleted, a protein called GCN2 signals cells to produce more fuel for growth. The team reasoned that a drug that shuts down GCN2 would render the cancer unable to produce enough fuel to survive.

“We were only partially right,” said Staschke, who is also an investigator in the Experimental and Developmental Therapeutics Research program at the IU Melvin and Bren Simon Comprehensive Cancer Center. “Inhibiting GCN2 did slow the growth of tumor cells, but it didn’t kill them. That’s when we discovered that cancer had a backup plan.”

The team then showed that a protein called p53 was the “Plan B” of cancer. p53, which is functionally retained in most prostate cancers, unlike other forms of cancer, signals to restrict cell division and bring together nutrients. Prostate cancers could be effectively destroyed when researchers inhibited both GCN2 and p53.

“The current study exploits the metabolic vulnerabilities unique to prostate cancer to deprive it of essential nutrients and kill these tumor cells,” Staschke said.

This research was carried out by graduate students Ricardo Cordova and Noah Sommers in collaboration with Jeffrey Brault, Ph.D., of the IU School of Medicine; Roberto Pili, MD, of the University at Buffalo; and Tracy Anthony, Ph.D., of Rutgers University.