Novel therapeutic agents for treatment of endometrial cancer

Endometrial cancer is a female genital cancer that occurs frequently in Europe and the United States. Conventional therapy for endometrial cancer does not permit fertility preservation or have effects on advanced and recurrent cancers, and new pharmacotherapies are needed. The fourth-generation progestin, dienogest, blocks excessive estrogenic activity and inhibits endometrial overgrowth. Metformin is an antidiabetic drug that may have an effect on endometrial cancer through targeting of the mammalian target of rapamycin (mTOR) pathway. mTOR inhibitors block cancer growth by arresting the cell cycle in G1 phase and clinical trials of new generation drugs with multiple sites of action in the mTOR pathway are underway. To inhibit down regulation of tumor suppressor genes by DNA hypermethylation and histone deacetylation, drugs targeting DNA methyltransferase (DNMT), microRNA (miRNA) and histone deacetylase (HDAC) are under development. AEZS-108 targeted to LHRH receptors on tumors is an effective compound for chemotherapy of endometrial cancer. In addition, targeting STAT3 or Wnt/β-catenin pathway by specific inhibitor in tumor cells and immunosuppressive cells, or along with other immunotherapy, might restore the immunocompetence of endometrial cancer patients. The oncogenic mechanisms underlying endometrial cancer, and regulatory factors based on the characteristics of endometrial cancer cells are gradually emerging. These data are likely to lead to development of new effective therapy for this disease.