Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Pharmacol Ther. 2021 Apr;220:107722. doi: 10.1016/j.pharmthera.2020.107722. Epub 2020 Nov 1.
Transcription factors (TFs) are major contributors to cancer risk and somatic development. In preclinical and clinical studies, direct or indirect inhibition of TF-mediated oncogenic gene expression profiles have proven to be effective in many tumor types, highlighting this group of proteins as valuable therapeutic targets. In spite of this, our understanding of TFs in epithelial ovarian cancer (EOC) is relatively limited. EOC is a heterogeneous disease composed of five major histologic subtypes; high-grade serous, low-grade serous, endometrioid, clear cell and mucinous. Each histology is associated with unique clinical etiologies, sensitivity to therapies, and molecular signatures - including diverse transcriptional regulatory programs. While some TFs are shared across EOC subtypes, a set of TFs are expressed in a histotype-specific manner and likely explain part of the histologic diversity of EOC subtypes. Targeting TFs present with unique opportunities for development of novel precision medicine strategies for ovarian cancer. This article reviews the critical TFs in EOC subtypes and highlights the potential of exploiting TFs as biomarkers and therapeutic targets.
转录因子 (TFs) 是癌症风险和体细胞发育的主要贡献者。在临床前和临床研究中，直接或间接抑制 TF 介导的致癌基因表达谱已被证明在许多肿瘤类型中有效，这凸显了这群蛋白质作为有价值的治疗靶点的重要性。尽管如此，我们对上皮性卵巢癌 (EOC) 中的 TFs 的了解相对有限。EOC 是一种由五种主要组织学亚型组成的异质性疾病；高级别浆液性、低级别浆液性、子宫内膜样、透明细胞和黏液性。每种组织学都与独特的临床病因、对治疗的敏感性和分子特征相关联——包括不同的转录调控程序。虽然一些 TFs 在 EOC 亚型中共享，但一组 TFs 以组织型特异性的方式表达，可能解释了 EOC 亚型组织学多样性的一部分。针对 TFs 为开发卵巢癌的新型精准医学策略提供了独特的机会。本文综述了 EOC 亚型中关键的 TFs，并强调了利用 TFs 作为生物标志物和治疗靶点的潜力。
