Repositioning GLP-1 Receptor Agonists in Endometrial Cancer: Molecular Rationale, Preclinical Insights, and...

Area of Science:

• Oncology
• Endocrinology
• Metabolic Syndrome

Background:

• Endometrial cancer (EC) incidence and mortality are increasing globally, linked to the obesity epidemic.
• Limited treatment options exist for obesity-associated, hormone-resistant, or fertility-preserving EC.
• Novel therapies targeting tumor biology and metabolic dysfunction are needed.

Purpose of the Study:

• To synthesize evidence on glucagon-like peptide-1 receptor (GLP-1R) agonists in endometrial cancer (EC).
• To evaluate their molecular rationale, preclinical data, population studies, and clinical trial evidence.
• To explore their potential in hormone-resistant and fertility-sparing EC.

Main Methods:

• Review of molecular mechanisms of GLP-1R signaling in endometrial tissues.
• Analysis of preclinical models demonstrating GLP-1R agonist effects.
• Examination of retrospective studies and ongoing clinical trials in EC.

Main Results:

• GLP-1R is expressed in EC tissues; activation influences cell proliferation, apoptosis, and autophagy.
• Preclinical data suggest GLP-1R agonists may restore progesterone receptor expression and enhance progestin therapy.
• Retrospective studies indicate potential benefits of combining GLP-1R agonists with local progestin therapy in high-risk women.

Conclusions:

• GLP-1R agonists represent a promising therapeutic strategy for EC, addressing both metabolic and tumor-intrinsic factors.
• Agent-specific differences and gastrointestinal tolerability require attention.
• Prospective, subtype-stratified trials are crucial to define their role in EC management, especially in fertility-sparing and adjuvant settings.