Research has identified a vulnerability in animal models of prostate cancer that deprives tumors of essential nutrients, potentially paving the way for new treatment options for this aggressive disease.
A team of scientists from the Indiana University School of Medicine has made a groundbreaking discovery regarding a vulnerability in animal models of prostate cancer. This vulnerability deprives prostate tumors of vital nutrients, hindering their growth and possibly leading to new treatment strategies for this serious illness.
Under the direction of Dr. Kirk Staschke, an assistant research professor of biochemistry and molecular biology, and Dr. Ronald C. Wek, a Showalter Professor of Biochemistry, the results of this study were recently published in Science Signaling.
Prostate cancer is one of the leading causes of cancer-related deaths among men in the U.S. Existing treatments primarily focus on blocking the hormone testosterone, which prostate cancer cells require for growth. However, many prostate tumors develop resistance to these therapies, leaving healthcare providers with limited options to combat the disease.
The research team found a promising new method to tackle prostate tumors by cutting off their supply of essential nutrients known as amino acids. Similar to other tumors, prostate cancer cells demand a significant amount of nutrients for their swift growth. When nutrients are low, a protein called GCN2 prompts the cells to produce more energy needed for their development. The researchers hypothesized that a drug that inhibits GCN2 would prevent the cancer cells from generating adequate energy to survive.
“We were partially right,” explained Staschke, who also participates in the Experimental and Developmental Therapeutics research program at the IU Melvin and Bren Simon Comprehensive Cancer Center. “While blocking GCN2 did decrease tumor cell growth, it did not eliminate them. That’s when we realized the cancer had a backup strategy.”
The research team discovered that the protein p53 served as cancer’s “Plan B.” In most prostate cancers, p53 remains functional — unlike in other types of cancer. It helps to limit cell division and accumulate nutrients. The researchers found that combining the inhibition of both GCN2 and p53 could effectively destroy prostate tumor cells.
“This study takes advantage of specific metabolic weaknesses in prostate cancer to deprive it of crucial nutrients, ultimately leading to the death of these tumor cells,” noted Staschke.
The study involved graduate students Ricardo Cordova and Noah Sommers, collaborating with Dr. Jeffrey Brault from IU School of Medicine, Dr. Roberto Pili from the University at Buffalo, and Dr. Tracy Anthony from Rutgers University. The research received funding from the National Institutes of Health, the U.S. Department of Defense, the American Cancer Society, and the IU Simon Comprehensive Cancer Center.
