子宫内膜癌的胞内分泌与靶向治疗

The Intracrinology and Targeted Therapy of Endometrial Cancer

基于外周组织中的细胞既能合成激素(肽类、蛋白类或类固醇类)又能对这些激素发生反应这一科学现象,19世纪末内分泌学的一个全新概念———“胞内分泌”被首次提出。外周非性腺组织(如子宫内膜)能合成各种酶类,包括类固醇硫酸酯酶(STS)、雌激素磺基转移酶(SULT1E1)、芳香化酶(CYP19A1)、17β-羟基类固醇脱氢酶(17β-HSD)等,利用循环中的类固醇前体物质,参与类固醇激素的局部合成与代谢(胞内分泌);在无孕激素拮抗的情况下,局部合成的雌激素持续刺激子宫内膜是子宫内膜癌发生、发展的高危因素。以雌激素的胞内分泌为作用靶点的靶向治疗药物,如CYP19A1抑制剂、STS抑制剂和1型HSD17B(HSD17B1)抑制剂等,能有效降低雌激素水平,用于子宫内膜癌的治疗。此类药物对其他雌激素依赖性疾病如子宫平滑肌瘤、子宫内膜增生、子宫内膜异位症等也有一定疗效。

Based on the scientific phenomenon that cells in peripheral tissues can synthesize and respond to hormones(peptides,proteins or steroids),a new concept of endocrinology-"intracrinology"was first proposed in the late 19th century.Peripheral tissues such as endometrium can express various enzymes including STS,SULT1E1,CYP19A1,17β-HSD,which utilize steroid precursors presenting in the blood to participate in the local synthesis and metabolism of steroid hormones(intracrinology).In the absence of progesterone antagonism,sustained stimulation of endometrium by locally synthesized estrogen is a high risk factor for the occurrence and development of endometrial cancer.Drugs targeting the local estrogen metabolism in the peripheral tissues,such as aromatase inhibitors,STS inhibitors and inhibitors of HSD17B1 can effectively reduce serum estrogen level and thus can be used as therapeutic agents against endometrial cancer.These drugs also have a certain effect on other estrogen-dependent diseases such as uterine leiomyoma,endometrial hyperplasia and endometriosis.