Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide. Tumorigenesis involves a multistep process resulting from the interactions of genetic, epigenetic, and environmental factors. Genome-wide association studies and sequencing studies have identified many epigenetic alterations associated with the development of lung cancer. Epigenetic mechanisms, mainly including DNA methylation, histone modification, and noncoding RNAs (ncRNAs), are heritable and reversible modifications that are involved in some important biological processes and affect cancer hallmarks. We summarize the major epigenetic modifications in lung cancer, focusing on DNA methylation and ncRNAs, their roles in tumorigenesis, and their effects on key signaling pathways. In addition, we describe the clinical application of epigenetic biomarkers in the early diagnosis, prognosis prediction, and oncotherapy of lung cancer. Understanding the epigenetic regulation mechanism of lung cancer can provide a new explanation for tumorigenesis and a new target for the precise treatment of lung cancer.
Highlights
Cancer is a major public health problem worldwide and is the second leading cause of death in the United States
nonsmall cell lung cancer (NSCLC) can be classified into lung adenocarcinoma (LUAD), which is the most prevalent form (40%), followed by lung squamous cell carcinoma (LUSC) (25%) and large cell carcinoma, which represents only 10% of the cases [3]
Current treatments targeting chromatin regulators approved by the Food and Drug Administration (FDA) include histone deacetylase inhibitors (HDACi), DNA methyltransferase inhibitors (DNMTi), and Janus kinase 2 inhibitors [11]
Summary
With the development of high-throughput sequencing technology, molecular targeted therapy has been widely used in patients with advanced lung cancer. Molecular targeted therapy can significantly improve patient progression-free survival compared with standard chemotherapy [6]. The frequency of KRAS mutations in LUAD seems constant across tumor grades, suggesting a role in tumor initiation or early tumorigenesis. Mutations in these genes may affect gene expression, thereby promoting the development of lung cancer. Epigenetic mechanisms are heritable and reversible, including DNA methylation, histone modifications, chromatin organization, and noncoding RNAs. A large number of studies have shown that epigenetics plays an important role in the development of lung cancer. We describe the clinical application of epigenetic biomarkers in the early diagnosis, prognosis prediction, and oncotherapy of lung cancer
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