表观遗传学
表观遗传疗法
DNA甲基化
肺癌
肺癌的治疗
癌症研究
癌症
免疫疗法
癌变
医学
肿瘤科
生物
生物信息学
内科学
遗传学
基因表达
基因
作者
M. Duruisseaux,Manel Esteller
标识
DOI:10.1016/j.semcancer.2017.09.005
摘要
Lung cancer is the leading cause of cancer-related mortality worldwide. Advances in our understanding of the genomics of lung cancer have led to substantial progress in the treatment of specific molecular subsets. Immunotherapy also emerges as a major breakthrough in lung cancer treatment. However, challenges remain as a consensual approach for early lung cancer detection remains elusive while primary or secondary drug resistance eventually leads to treatment failure in all patients with advanced disease. Furthermore, a large portion of patients are still treated with conventional chemotherapy that is only modestly effective. The last two decades have seen exponential developments in the epigenetic understanding of lung cancer. Epigenetic alterations in DNA methylation, non-coding RNA expression, chromatin modeling and post transcriptional regulators are key events in each step of lung cancer pathogenesis. Here, we review the central role epigenetic disruptions play in lung cancer carcinogenesis and the acquisition of cancerous phenotype and aggressive behavior as well as in the resistance to therapy. Epigenetic disruptions could represent reliable biomarkers for lung cancer risk assessment, early diagnosis, prognosis stratification, molecular classification and prediction of treatment efficacy. The therapeutic potential of epigenetics targeted drugs in combination with chemotherapy, targeted therapy and/or immunotherapy is currently being intensively investigated. We suggest that integration of tissue-derived or circulating epigenetic biomarkers and epidrugs in clinical trial design will translate epigenetic knowledge of lung cancer into the clinic and improve lung cancer patient outcomes.
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