Dr Krause on GLP-1 Receptor Agonist Therapy in Endometrial Cancer

Danielle Krause, MD, gynecologic oncology fellow, the University of Oklahoma (OU), OU Health, Stephenson Cancer Center, discusses findings from a preclinical study investigating the effects of GLP-1 receptor agonist therapy in endometrial cancer cell lines and mouse models.

Krause states that this study obtained compelling results. Firstly, the in vitro investigations of GLP-1 receptor agonist therapy aligned with and substantiated results from preliminary studies, she explains. Although it's established that GLP-1 receptors are present in various bodily tissues, notably the liver and pancreas, investigators in this trial explored the presence of GLP-1 receptors on the endometrium, Krause explains. An initial analysis of GLP-1 receptor expression revealed an elevation, both at the mRNA and protein levels, in patients with endometrial cancer compared with those with benign endometrium. Notably, as the cancers progressed through stages, the GLP-1 expression levels increased, indicating a potential actionable target in the management of endometrial cancer, she emphasizes.

Subsequently, GLP-1 receptor agonists had a discernible impact on endometrial cancer cell growth, Krause emphasizes. Although no explicit signs of cell death were observed, there was a noticeable decrease in cell proliferation, indicating a potential avenue for therapeutic intervention in various types of cancers, she elucidates.

Perhaps most reassuringly, especially given the prevalent use of progesterone therapy in patients with endometrial cancer, combination treatment involving GLP-1 receptor agonists did not compromise the well-known effects of progesterone in endometrial cancer cells, Krause continues. This crucial finding was validated in animal studies, where the combined treatment approach retained the growth-suppressing and cell death–inducing effects of progesterone, she says. Notably, the mice that received the combination therapy exhibited less weight gain than those receiving progesterone alone, mitigating a known adverse effect associated with progesterone therapy, Krause emphasizes.

This study has revealed that GLP-1 receptors are a potential therapeutic target in endometrial cancer, Krause concludes.