Circulating epigenetic biomarkers in lung malignancies: From early diagnosis to therapy.

Lung cancer (LC) and malignant mesothelioma (MM) are malignancies linked to environmental/occupational exposure, which are increasing in incidence. Despite advances in chemotherapy, radiation therapy and surgical management of LC and MM, the median survival remains less than 12 months. Early detection represents one of the most promising approaches to reducing the growing cancer burden by increasing chemotherapy treatment efficiency. At present, early diagnosis is rather difficult and depends on invasive sampling of pleural fluid or tissue. Currently the most widely used screening method for the surveillance of exposed subjects is computed tomography (CT), which is costly, exposes patients to repeated high doses of radiation, and typically detects the malignancy at its advanced stage. Recently, a virtually non-invasive 'liquid biopsy' has emerged as source to characterize tumour heterogeneity. The genetic/epigenetic changes during tumour evolution can be detected in fluids and used as cancer biomarkers. Therefore, increasingly interest has been paid to circulating (cell-free) nucleic acids (cfDNA/cfmiRNAs) epigenetically modulated during cell transformation. Hypermethylation of tumour suppressor genes is frequently observed in cancers, and such epigenetic changes are potential markers for detecting and monitoring tumours. The same predictive biomarkers can be used as therapy targets.