Tirzepatide as an innovative treatment strategy in a pre-clinical model of obesity-driven endometrial cancer
Interventions that combat obesity and its associated metabolic perturbations may decrease incidence and improve outcomes of endometrial cancer (EC). Potential options for weight loss include pharmacotherapeutic interventions such as tirzepatide, a dual-acting glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptor agonist. Given this, we explored the anti-obesity and anti-tumorigenic effects of tirzepatide in our pre-clinical mouse model of endometrioid EC. Starting at 4 weeks of age, Lkb1 Both obese and lean mice began to lose body weight after 2 weeks of tirzepatide treatment, ultimately achieving a significant weight loss of 20.1 % in obese mice and 16.8 % in lean mice. Tirzepatide improved obesity-induced serum adiponectin, leptin, GIP, and C-reactive protein levels. Furthermore, tirzepatide relative to vehicle, effectively reduced tumor growth in obese and lean mice, inhibited the ErbB signaling and glycolysis/gluconeogenesis in tumors of obese mice, and increased O-linked glycosylation biosynthesis and phospholipase D signaling in tumors of lean mice. Tirzepatide decreased both mouse weight and tumor growth via effects on metabolic and immune pathways in the EC tumors that differed between obese and lean mice. This novel weight loss treatment deserves further evaluation as an innovative strategy in the management of EC.