The Molecular Biology of Endometrial Cancers and the Implications for Pathogenesis, Classification, and Targeted Therapies
The Molecular Biology of Endometrial Cancers and the Implications for Pathogenesis, Classification, and Targeted Therapies
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DOI：
10.1177/107327480901600102
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发表时间：
2009-01-01
期刊：
影响因子：
2.6
通讯作者：
Wenham, Robert M.
中科院分区：
文献类型：
--
作者：
Bansal, Nisha;Yendluri, Vimala;Wenham, Robert M.
背景：了解和识别子宫内膜癌的分子生物学和遗传学是开发新疗法的核心。本文综述了子宫内膜癌发生的分子基础，发病机制，分类，和靶向治疗的影响。方法：基因和细胞通路，可能有一个重要的作用，在子宫内膜癌，子宫内膜样癌和非子宫内膜样癌，确定。本文综述了近年来针对这些基因和通路的药物研究进展和潜在的药物靶点。PI 3CA和K-ras突变不太常见，但通常与PTEN相关。MLH 1和MSH 6的改变与微卫星不稳定性有关。β-连环蛋白有轻微但重要的关联。相反，p53突变更常与非乳腺癌相关;其他突变是p16失活和/或HER-2/neu过表达。E-钙粘蛋白的缺乏在非胶质瘤样癌中更常见，并与预后不良相关。靶向AKT-PI 3 K-mTOR通路和抑制表皮生长因子受体（EGFR）、血管内皮生长因子（VEGF）、成纤维细胞生长因子受体2（FGFR 2）和叶酸受体的新型药物目前正在研究中。
Background: Understanding and identifying molecular biology and genetics of endometrial cancer are central to the development of novel therapies. This article reviews the molecular basis for genesis of endometrial cancer with regard to pathogenesis, classification, and implications for targeted therapies.Methods: Genes and cellular pathways that may have an important role in endometrial cancers, both endometrioid and nonendometrioid cancers, are identified. Recently studied drugs and potential future drugs that target some of these genes and pathways are reviewed.Results: The most frequent genetic alteration of endometrioid endometrial cancer is PTEN. PI3CA and K-ras mutations are less common but are often associated with PTEN. Alterations in MLH1 and MSH6 are documented with microsatellite instability. beta-catenin has a minor but significant association. Conversely, p53 mutation is more often associated with nonendometrioid cancer; others being inactivation of p16 and/or overexpression of HER-2/neu. Absence of E-cadherin is more often than not present in nonendometrioid cancers and is associated with poor prognosis. Novel agents that target the AKT-PI3K-mTOR pathway and those that inhibit epidermal growth factor receptor (EGFR), vascular endothelial growth factors (VEGF), fibroblast growth factor receptor 2 (FGFR2), and folate receptors are currently being investigated.Conclusions: Novel targeted agents, either alone or in combination with cytotoxic agents, may result in superior treatment for patients.