Hormone Therapy plus mTOR Inhibitors in the Treatment of Endometrial Carcinoma

Hormonal therapies, such as progestins, exhibit only limited efficacy in treating advanced endometrial cancer. The mechanisms underlying resistance to progestin therapy remain poorly understood. However, activation of the PI3K/AKT/mTOR signaling pathway has been linked to this resistance. Alterations in components of this pathway, including inactivating mutations in PTEN, activating mutations in PIK3CA, and mutations in PIK3R1, are commonly observed in endometrial carcinomas. mTOR inhibitors, such as temsirolimus, everolimus, and ridaforolimus, have shown activity against endometrial cancer. This has led to growing interest in combining hormonal therapy with mTOR inhibitors, as both approaches demonstrate individual efficacy, with the hypothesis that mTOR inhibition may enhance the effectiveness of hormonal treatments.