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针对食管癌的表观遗传失调进行靶向治疗:最新进展和新兴方法。

Targeting epigenetic deregulations for the management of esophageal carcinoma: recent advances and emerging approaches.

机构信息

Department of Genetics, Maharshi Dayanand University, (Haryana), Rohtak, 124001, India.

Department of Internal Medicine, Pt. B.D, Sharma University of Health Sciences, (Haryana), Rohtak, 124001, India.

出版信息

Cell Biol Toxicol. 2023 Dec;39(6):2437-2465. doi: 10.1007/s10565-023-09818-5. Epub 2023 Jun 20.

Abstract

Ranking from seventh in incidence to sixth in mortality, esophageal carcinoma is considered a severe malignancy of food pipe. Later-stage diagnosis, drug resistance, and a high mortality rate contribute to its lethality. Esophageal squamous cell carcinoma and esophageal adenocarcinoma are the two main histological subtypes of esophageal carcinoma, with squamous cell carcinoma alone accounting for more than eighty percent of its cases. While genetic anomalies are well known in esophageal cancer, accountability of epigenetic deregulations is also being explored for the recent two decades. DNA methylation, histone modifications, and functional non-coding RNAs are the crucial epigenetic players involved in the modulation of different malignancies, including esophageal carcinoma. Targeting these epigenetic aberrations will provide new insights into the development of biomarker tools for risk stratification, early diagnosis, and effective therapeutic intervention. This review discusses different epigenetic alterations, emphasizing the most significant developments in esophageal cancer epigenetics and their potential implication for the detection, prognosis, and treatment of esophageal carcinoma. Further, the preclinical and clinical status of various epigenetic drugs has also been reviewed.

摘要

食管癌的发病率位居第七,死亡率位居第六,被认为是一种严重的食管恶性肿瘤。晚期诊断、耐药性和高死亡率使其具有致命性。食管癌的两种主要组织学亚型是食管鳞状细胞癌和食管腺癌,其中鳞状细胞癌单独占其病例的 80%以上。虽然食管癌中已知存在遗传异常,但近二十年来也在探索表观遗传失调的责任。DNA 甲基化、组蛋白修饰和功能非编码 RNA 是参与不同恶性肿瘤(包括食管癌)调节的关键表观遗传因子。针对这些表观遗传异常将为开发风险分层、早期诊断和有效治疗干预的生物标志物工具提供新的见解。本文综述了不同的表观遗传改变,强调了食管癌表观遗传学的最重要进展及其对食管癌检测、预后和治疗的潜在意义。此外,还回顾了各种表观遗传药物的临床前和临床现状。

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