表观遗传学
DNA甲基化
生物
免疫疗法
癌变
表观遗传疗法
疾病
癌症
生物信息学
癌症研究
转移
表观遗传学
肺癌
医学
肿瘤科
遗传学
病理
基因表达
基因
作者
Parvez Khan,Jawed A. Siddiqui,Shailendra Kumar Maurya,Imayavaramban Lakshmanan,Maneesh Jain,Apar Kishor Ganti,Ravi Salgia,Surinder K. Batra,Mohd W. Nasser
标识
DOI:10.1016/j.semcancer.2020.11.006
摘要
Small cell lung cancer (SCLC) is a particular subtype of lung cancer with high mortality. Recent advances in understanding SCLC genomics and breakthroughs of immunotherapy have substantially expanded existing knowledge and treatment modalities. However, challenges associated with SCLC remain enigmatic and elusive. Most of the conventional drug discovery approaches targeting altered signaling pathways in SCLC end up in the 'grave-yard of drug discovery', which mandates exploring novel approaches beyond inhibiting cell signaling pathways. Epigenetic modifications have long been documented as the key contributors to the tumorigenesis of almost all types of cancer, including SCLC. The last decade witnessed an exponential increase in our understanding of epigenetic modifications for SCLC. The present review highlights the central role of epigenetic regulations in acquiring neoplastic phenotype, metastasis, aggressiveness, resistance to chemotherapy, and immunotherapeutic approaches of SCLC. Different types of epigenetic modifications (DNA/histone methylation or acetylation) that can serve as predictive biomarkers for prognostication, treatment stratification, neuroendocrine lineage determination, and development of potential SCLC therapies are also discussed. We also review the utility of epigenetic targets/epidrugs in combination with first-line chemotherapy and immunotherapy that are currently under investigation in preclinical and clinical studies. Altogether, the information presents the inclusive landscape of SCLC epigenetics and epidrugs that will help to improve SCLC outcomes.
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