Ribeiro Jennifer R, Freiman Richard N
Brown University, Pathobiology Graduate Program, 70 Ship St., Providence, RI 02903, USA.
Brown University, Pathobiology Graduate Program, 70 Ship St., Providence, RI 02903, USA; Brown University, Department of Molecular and Cellular Biology and Biochemistry, 70 Ship St., Providence, RI 02903, USA.
J Steroid Biochem Mol Biol. 2014 Sep;143:160-73. doi: 10.1016/j.jsbmb.2014.02.010. Epub 2014 Feb 22.
Resistance to anti-estrogen therapies is a prominent challenge in the treatment of ovarian cancer. Tumors develop endocrine resistance by acquiring adaptations that help them rely on alternative oncogenic signaling cascades, which crosstalk with estrogen signaling pathways. An understanding of estrogen signaling crosstalk with these growth promoting cascades is essential in order to maximize efficacy of anti-estrogen treatments in ovarian cancer. Herein, we provide an overview of estrogen signaling in ovarian cancer and discuss the major challenges associated with anti-estrogen therapies. We also review what is currently known about how genomic and non-genomic estrogen signaling pathways crosstalk with several major oncogenic signaling cascades. The insights provided here illustrate existing strategies for targeting endocrine resistant ovarian tumors and may help identify new strategies to improve the treatment of this disease.
抗雌激素疗法的耐药性是卵巢癌治疗中的一个突出挑战。肿瘤通过获得适应性改变来产生内分泌耐药性,这些适应性改变有助于它们依赖替代致癌信号级联反应,而这些信号级联反应与雌激素信号通路相互作用。了解雌激素信号与这些促进生长的级联反应之间的相互作用对于最大化抗雌激素治疗在卵巢癌中的疗效至关重要。在此,我们概述了卵巢癌中的雌激素信号,并讨论了与抗雌激素疗法相关的主要挑战。我们还回顾了目前已知的基因组和非基因组雌激素信号通路如何与几种主要致癌信号级联反应相互作用的情况。这里提供的见解阐述了针对内分泌耐药性卵巢肿瘤的现有策略,并可能有助于确定改善这种疾病治疗的新策略。