Molecular epigenetics in the management of ovarian cancer: are we investigating a rational clinical promise?
Molecular epigenetics in the management of ovarian cancer: are we investigating a rational clinical promise?
复制标题
DOI：
10.3389/fonc.2014.00071
复制
发表时间：
2014
影响因子：
4.7
通讯作者：
Murph MM
中科院分区：
文献类型：
--
作者：
Nguyen HT;Tian G;Murph MM
表观遗传学本质上是基因表达的表型变化，而没有任何DNA序列的改变;表观遗传学在癌症研究和主流肿瘤学中的出现为新的希望提供了动力。然而，目前尚不清楚这些知识是否会转化为改善卵巢癌的临床管理。在这种恶性肿瘤中，女性仍在接受类似于1978年批准的化疗，这是迄今为止治疗卵巢癌的最大突破之一。虽然液体肿瘤受益于表观遗传学相关疗法，但卵巢癌等实体肿瘤（尚未？）。在此，我们将回顾分子表观遗传学，特别是DNA甲基化，组蛋白修饰和microRNA，但也包括转录因子，因为它们在卵巢癌中也很重要。还总结了表观遗传修饰作用的临床前和临床研究。不幸的是，卵巢癌在很大程度上仍然是一种特发性疾病，并且有许多患者管理领域可以从改进的技术中受益。这篇综述也将强调证据表明，表观遗传学可能有临床前的药理学和临床应用的预后和诊断。最后，目前在临床试验中的药物（即，组蛋白去乙酰化酶抑制剂）与表观遗传学在利用化学抗性中的前景一起沿着讨论。表观遗传学最终是否会成为卵巢癌更好管理的答案目前尚不清楚;但我们希望将来会如此。
Epigenetics is essentially a phenotypical change in gene expression without any alteration of the DNA sequence; the emergence of epigenetics in cancer research and mainstream oncology is fueling new hope. However, it is not yet known whether this knowledge will translate to improved clinical management of ovarian cancer. In this malignancy, women are still undergoing chemotherapy similar to what was approved in 1978, which to this day represents one of the biggest breakthroughs for treating ovarian cancer. Although liquid tumors are benefiting from epigenetically related therapies, solid tumors like ovarian cancer are not (yet?). Herein, we will review the science of molecular epigenetics, especially DNA methylation, histone modifications and microRNA, but also include transcription factors since they, too, are important in ovarian cancer. Pre-clinical and clinical research on the role of epigenetic modifications is also summarized. Unfortunately, ovarian cancer remains an idiopathic disease, for the most part, and there are many areas of patient management, which could benefit from improved technology. This review will also highlight the evidence suggesting that epigenetics may have pre-clinical utility in pharmacology and clinical applications for prognosis and diagnosis. Finally, drugs currently in clinical trials (i.e., histone deacetylase inhibitors) are discussed along with the promise for epigenetics in the exploitation of chemoresistance. Whether epigenetics will ultimately be the answer to better management in ovarian cancer is currently unknown; but we hope so in the future.