Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain and Centro de Investigación Biomédica en Red de Cáncer (CIBERONC); Department of Respiratory Medecine, Hôpital Louis-Pradel, Hospices civils de Lyon, 28 avenue du Doyen Lépine, 69677, Lyon cedex, France.
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain and Centro de Investigación Biomédica en Red de Cáncer (CIBERONC); Instituciò Catalana de Recerca i Estudis Avançats (ICREA), 08010, Barcelona, Catalonia, Spain; Department of Physiological Sciences II, School of Medicine, University of Barcelona, 08036, Barcelona, Catalonia, Spain.
Semin Cancer Biol. 2018 Aug;51:116-128. doi: 10.1016/j.semcancer.2017.09.005. Epub 2017 Sep 14.
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.
肺癌是全球癌症相关死亡的主要原因。我们对肺癌基因组学的理解的进步导致了特定分子亚群治疗的重大进展。免疫疗法也成为肺癌治疗的重大突破。然而，挑战依然存在，因为一致的早期肺癌检测方法仍然难以捉摸，而原发性或继发性药物耐药性最终导致所有晚期疾病患者的治疗失败。此外，还有很大一部分患者仍接受常规化疗，而常规化疗的疗效仅适度。在过去的二十年中，人们对肺癌的表观遗传学理解取得了指数级的发展。DNA 甲基化、非编码 RNA 表达、染色质建模和转录后调节剂的表观遗传改变是肺癌发病机制的每个步骤中的关键事件。在这里，我们回顾了表观遗传破坏在肺癌发生癌、获得癌症表型和侵袭性行为以及对治疗的耐药性中所起的核心作用。表观遗传破坏可能是肺癌风险评估、早期诊断、预后分层、分子分类和治疗效果预测的可靠生物标志物。目前正在深入研究针对表观遗传学的靶向药物与化疗、靶向治疗和/或免疫疗法联合治疗的治疗潜力。我们建议将组织衍生或循环的表观遗传生物标志物和表型药物整合到临床试验设计中，将肺癌的表观遗传学知识转化为临床实践，改善肺癌患者的预后。
