Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Oncol Rep. 2013 Mar;29(3):855-60. doi: 10.3892/or.2013.2221. Epub 2013 Jan 3.
Cases of endometrial cancer have increased in recent years, but the prognosis of patients with this disease has also been improved by combined modality therapy with surgery, radiotherapy and chemotherapy. However, the development of new therapy is required from the perspectives of conservation of fertility and efficacy for recurrent and intractable cancer. New candidate therapeutic agents for endometrial cancer include fourth-generation progestins for inhibition of growth and differentiation of endometrial glands; metformin for reduction of hTERT expression in the endometrium and inhibition of the mTOR pathway by activation of AMPK, with consequent inhibition of the cell cycle; mTOR inhibitors for supressing growth of cancer cells by G1 cell cycle arrest; microRNAs involved in the molecular mechanisms of oncogenesis and progression; and HDAC inhibitors that block the growth of cancer cells by transcriptional elevation of tumor-suppressor genes, cell cycle arrest and induction of apoptosis. In this study, we review the background and early clinical evidence for these agents as new therapeutic candidates for endometrial cancer.
近年来，子宫内膜癌的病例有所增加，但通过手术、放疗和化疗相结合的综合治疗，该病患者的预后也得到了改善。然而，从保留生育能力和治疗复发性、难治性癌症的疗效的角度来看，需要开发新的治疗方法。子宫内膜癌的新候选治疗药物包括第四代孕激素，用于抑制子宫内膜腺体的生长和分化；二甲双胍通过激活 AMPK 减少子宫内膜中 hTERT 的表达，并抑制 mTOR 通路，从而抑制细胞周期；mTOR 抑制剂通过 G1 细胞周期阻滞抑制癌细胞生长；涉及肿瘤发生和进展分子机制的 microRNAs；以及 HDAC 抑制剂通过转录上调肿瘤抑制基因、细胞周期阻滞和诱导细胞凋亡来阻止癌细胞生长。在本研究中，我们回顾了这些药物作为子宫内膜癌新的治疗候选药物的背景和早期临床证据。
