**6. The role of molecular-target therapy in management of endometrial**

As opposed to conventional cytotoxic drugs, molecular-targeted cytotoxic drugs are able to differentiate between normal cells and cancerous cells, and therefore specifically damage only the cancerous cells by inhibiting the cellular molecules/pathways associated with neoplastic proliferation and metastasis [109].

## **6.1. Mammalian target of rapamycin (mTOR) inhibitors**

PTEN genetic mutations are associated with reduced apoptosis and are implicated in more than 80% of endometrioid cancer of the uterus [109]. The effects of PTEN genetic muta‐ tions can be decreased by utilizing mammalian target of rapamycin (mTOR) inhibitors (for example, temsirolimus, ridaforolimus, everolimus, and AP2357) by interrupting phosphoi‐ nositide 3-kinase̸AKT̸mTOR pathway [109, 110]. In a phase II clinical trial of temsiroli‐ mus in previously chemotherapy-untreated patients with recurrent endometrial cancer, 26% and 63% of patients experienced partial response and stable disease, respectively [111]. In a phase II clinical trial of temsirolimus in previously chemotherapy-treated patients with recurrent endometrial cancer, 7% and 44% of patients experienced partial response and stable disease, respectively [112].

In a phase II clinical trial of ridaforolimus as a single agent in patients with advanced endo‐ metrial cancer, a total 29% of patients experienced clinical beneficial response in the form of complete response, partial response or prolonged stable disease for more than 16 weeks [113].

In a phase II clinical trial of everolimus as a single agent in patients with recurrent endometrial cancer, 21% of patients experienced confirmed clinical beneficial response in the form of complete response, partial response or prolonged stable disease at 20 weeks after therapy [114].

There is an ongoing randomized controlled trial single-agent temsirolimus versus a combina‐ tion of temsirolimus and hormonal therapy [109]
