Epigenetics of colorectal cancer: biomarker and therapeutic potential.,Nature Reviews Gastroenterology & Hepatology

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Epigenetics of colorectal cancer: biomarker and therapeutic potential.
Nature Reviews Gastroenterology & Hepatology ( IF 45.9 ) Pub Date : 2020-01-03 , DOI: 10.1038/s41575-019-0230-y
Gerhard Jung _{1,

2} , Eva Hernández-Illán _{1,

2} , Leticia Moreira _{1,

2} , Francesc Balaguer _{1,

2} , Ajay Goel _{3,

4}

Affiliation

Colorectal cancer (CRC), a leading cause of cancer-related death worldwide, evolves as a result of the stepwise accumulation of a series of genetic and epigenetic alterations in the normal colonic epithelium, leading to the development of colorectal adenomas and invasive adenocarcinomas. Although genetic alterations have a major role in a subset of CRCs, the pathophysiological contribution of epigenetic aberrations in this malignancy has attracted considerable attention. Data from the past couple of decades has unequivocally illustrated that epigenetic marks are important molecular hallmarks of cancer, as they occur very early in disease pathogenesis, involve virtually all key cancer-associated pathways and, most importantly, can be exploited as clinically relevant disease biomarkers for diagnosis, prognostication and prediction of treatment response. In this Review, we summarize the current knowledge on the best-studied epigenetic modifications in CRC, including DNA methylation and histone modifications, as well as the role of non-coding RNAs as epigenetic regulators. We focus on the emerging potential for the bench-to-bedside translation of some of these epigenetic alterations into clinical practice and discuss the burgeoning evidence supporting the potential of emerging epigenetic therapies in CRC as we usher in the era of precision medicine.

中文翻译：

结直肠癌的表观遗传学：生物标志物和治疗潜力。

结直肠癌 (CRC) 是全球癌症相关死亡的主要原因，其演变是由于正常结肠上皮细胞中一系列遗传和表观遗传改变的逐步积累，导致结直肠腺瘤和浸润性腺癌的发展。尽管遗传改变在一部分 CRC 中起主要作用，但表观遗传畸变在这种恶性肿瘤中的病理生理学贡献已引起相当大的关注。过去几十年的数据明确表明，表观遗传标记是癌症的重要分子标志，因为它们发生在疾病发病机制的早期，涉及几乎所有关键的癌症相关途径，最重要的是，可以用作临床相关的疾病生物标志物用于诊断，治疗反应的预后和预测。在这篇综述中，我们总结了目前在 CRC 中研究得最好的表观遗传修饰的知识，包括 DNA 甲基化和组蛋白修饰，以及非编码 RNA 作为表观遗传调节因子的作用。我们专注于将这些表观遗传改变中的一些转化为临床实践的新兴潜力，并讨论支持新兴表观遗传疗法在 CRC 中的潜力的新兴证据，因为我们迎来了精准医学时代。

更新日期：2020-01-04

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