Estrogen biosynthesis and action in ovarian cancer.
Estrogen biosynthesis and action in ovarian cancer.
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DOI：
10.3389/fendo.2014.00192
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发表时间：
2014
影响因子：
5.2
通讯作者：
Thalhammer T
中科院分区：
文献类型：
--
作者：
Mungenast F;Thalhammer T
卵巢癌仍然是全世界妇女中最致命的妇科恶性肿瘤。这归因于这些肿瘤的两个主要特征，即(i)在肿瘤晚期诊断，以及（ii）在最初成功使用铂和紫杉醇衍生物治疗后迅速开始对标准化疗产生耐药性。因此，迫切需要为这些肿瘤的早期诊断和更好的治疗选择提供新的靶点。流行病学资料显示，卵巢癌的诱导和生物学与终生雌激素暴露有关。此外，实验数据显示，卵巢癌细胞与其他激素依赖性癌症（如乳腺癌和子宫内膜癌）共享许多雌激素调节途径。然而，卵巢癌是一种异质性疾病，其亚型在突变、起源、行为、标志物和预后方面存在很大差异，对标准化疗的反应也不同。因此，卵巢癌亚型的特征可能会导致对各种亚型的更好的治疗选择，特别是对最常见的高级别浆液性卵巢癌。为此，有必要进一步研究卵巢癌细胞中雌激素相关通路和雌激素形成。本文综述了卵巢癌亚型的研究概况，并阐述了雌激素在卵巢癌中的作用。此外，还描述了合成和代谢雌激素的活性酶，并讨论了针对这些途径的策略。
Ovarian cancer is still the deadliest of all gynecologic malignancies in women worldwide. This is attributed to two main features of these tumors, namely, (i) a diagnosis at an advanced tumor stage, and, (ii) the rapid onset of resistance to standard chemotherapy after an initial successful therapy with platin- and taxol-derivatives. Therefore, novel targets for an early diagnosis and better treatment options for these tumors are urgently needed. Epidemiological data show that induction and biology of ovarian cancer is related to life-time estrogen exposure. Also experimental data reveal that ovarian cancer cells share a number of estrogen regulated pathways with other hormone-dependent cancers, e.g., breast and endometrial cancer. However, ovarian cancer is a heterogeneous disease and the subtypes are quite different with respect to mutations, origins, behaviors, markers, and prognosis and respond differently to standard chemotherapy. Therefore, a characterization of ovarian cancer subtypes may lead to better treatment options for the various subtypes and in particular for the most frequently observed high-grade serous ovarian carcinoma. For this intention, further studies on estrogen-related pathways and estrogen formation in ovarian cancer cells are warranted. The review gives an overview on ovarian cancer subtypes and explains the role of estrogen in ovarian cancer. Furthermore, enzymes active to synthesize and metabolize estrogens are described and strategies to target these pathways are discussed.
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