GLP-1 Agonists May One Day Treat Prostate Cancer

Diabetes, weight loss and now possibly cancer. Glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal cells that leads to insulin secretion through the GLP-1 receptor. Available therapies that target GLP-1 are known for their roles in treating diabetes and obesity and reducing the risk of cardiovascular disease.

One day, GLP-1 agonists might even be used to treat prostate cancer. Several recent studies have highlighted the role of GLP-1 in prostate cancer, giving hope that this could present a new way to treat this disease.

The most recent study is a poster presented at the American Urology Association’s annual meeting on May 3, 2024, to May 6, 2024. Researchers found higher GLP-1 receptor gene expression with basal prostate cancer, a rare type of prostate cancer that can present with normal prostate-specific antigen (PSA) levels.

Mohammed Shahait, MBBS

Researchers, led by Mohammed Shahait, MBBS, of the School of Medicine at University of Sharjah in Dubai, wanted to assess GLP-1 receptor and glucagon/GLP-1 gene expression in prostate specimens and determine whether there was correlation with baseline clinical variables.

They assessed deidentified clinical and transcriptome data from the Decipher Genomics Resource for Intelligent Discovery (GRID) database from Veracyte in San Diego. Baseline clinical and pathological factors and a panel of 22 transcriptomic signatures were examined.

They found higher GLP-1 gene expression was associated with the basal subtype of prostate cancer. Researchers said this lays the groundwork for clinical investigation of potential use of GLP-1 receptor agonists in prostate cancer.

Shahait said by email that he is currently writing a proposal for a clinical trial that would assess the role of GLP-1 agonists in prostate cancer.

Additionally, Shahait and his colleagues last month published a review paper in the journal Cancers, which described how GLP-1 interferes with cell growth and survival, including the possibility that GLP-1 plays a role in apoptosis, a type of cell death. In prostate cancer, GLP-1 triggers the enzyme adenylyl cyclase, which triggers various cell processes and pathways involved in various cancers.

This review also noted an increase in prostate cancer among those with metabolic syndrome, a condition with glucose intolerance, high blood pressure, high cholesterol levels. Metabolic syndrome is a risk factor for diabetes and cardiovascular disease. Researchers speculated the correlation of metabolic syndrome and risk of cancer may involve higher levels of insulin and growth hormones. Patients with prostate cancer and metabolic syndrome have shorter overall survival.

Researchers in the Cancers paper suggest that GLP-1 receptor agonists could be explored for use to prevent prostate cancer in those with metabolic syndrome or as an additional therapy with cancer treatments.

Separately, researchers from Australia published the results of very small study on GLP-1 and prostate cancer. Published in Endocrine Oncology in January 2024, researchers found that GLP-1 was expressed in metastatic prostate cancer. Researchers at Melbourne Health in Parkville, Australia, conducted a study with four patients with metastatic castrate-resistant prostate cancer (mCRPC), a very late stage of prostate cancer.

In this study, the patients received the GLP-1 exenatide, which is marketed as Bydureon in an extended-release formulation to treat diabetes. It binds to the GLP-1 receptor, and researchers said it has been used as a radionuclide carrier in PET/CT imaging. The researchers aimed to use exenatide before the scans to see if there was expression of GLP-1 in prostate cancer lesions.

These researchers confirmed that GLP-1 is expressed in prostate cancer, saying that this research contributed to the growing evidence that GLP-1 receptor agonists could be a treatment for prostate cancer.