University of Hawaii, John A. Burns School of Medicine, Honolulu, HI, USA.
Fam Cancer. 2011 Sep;10(3):469-72. doi: 10.1007/s10689-011-9471-9.
Peutz-Jeghers patients frequently develop clinically significant complications, namely hemorrhage and bowel obstruction, from small intestinal hamartomatous polyps that frequently require surgery. In addition, many PJS patients develop epithelial malignancies in a variety of organs. The vast majority of PJS is due to germline alterations in the STK11 gene that encodes a protein that modulates PI3-kinase signaling, a key regulator of cell survival and growth. One of the major downstream mediators of PI3-kinase signaling is mTOR, the mammalian target of rapamycin. Several drugs that inhibit the PI3-kinase signal transduction pathway are in development and one, RAD001 (everolimus), an mTOR inhibitor, was recently approved for the treatment of renal cell carcinoma. Effective chemoprevention of intestinal polyps would be a first step in simplifying and improving the management of PJS patients. We present here, the rationale for the first human PJS chemoprevention trial using an mTOR inhibitor.
皮杰特-杰格斯综合征（Peutz-Jeghers syndrome，PJS）患者常因小肠错构瘤性息肉而出现严重的临床并发症，如出血和肠梗阻，这些息肉通常需要手术治疗。此外，许多 PJS 患者还会在多种器官中发生上皮恶性肿瘤。绝大多数 PJS 是由于 STK11 基因突变引起的，该基因编码一种调节 PI3-激酶信号的蛋白，PI3-激酶信号是细胞存活和生长的关键调节剂。PI3-激酶信号通路的主要下游介质之一是 mTOR，即雷帕霉素的哺乳动物靶标。目前正在开发几种抑制 PI3-激酶信号转导通路的药物，其中一种，即 mTOR 抑制剂 RAD001（依维莫司），最近被批准用于治疗肾细胞癌。有效的肠息肉化学预防将是简化和改善 PJS 患者管理的第一步。我们在此介绍了首例使用 mTOR 抑制剂进行 PJS 化学预防试验的原理。
