And this prognosis benefit of MPA and metformin combination over MPA alone was more prominent for obese patients (BMI ≥ 25 kg/m2) than non-obese patients (BMI < 25 kg/m2) through inhibiting the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mTOR pathway by activating AMPK, a master regulator of cellular energy homeostasis AMPK and the PI3K-AKT-mTOR pathway is known as one of the most commonly dysregulated signaling pathways in endometrial cancer [23]. The gene discussed is AKT1; the disease is endometrial cancer.