title: Epigenetic therapy approaches in non-small cell lung cancer: Update and perspectives.
abstract: Non-small cell lung cancer (NSCLC) still constitutes the most common cancer-related cause of death worldwide. All efforts to introduce suitable treatment options using chemotherapeutics or targeted therapies have, up to this point, failed to exhibit a substantial effect on the 5-year-survival rate. The involvement of epigenetic alterations in the evolution of different cancers has led to the development of epigenetics-based therapies, mainly targeting DNA methyltransferases (DNMTs) and histone-modifying enzymes. So far, their greatest success stories have been registered in hematologic neoplasias. As the effects of epigenetic single agent treatment of solid tumors have been limited, the investigative focus now lies on combination therapies of epigenetically active agents with conventional chemotherapy, immunotherapy, or kinase inhibitors. This review includes a short overview of the most important preclinical approaches as well as an extensive discussion of clinical trials using epigenetic combination therapies in NSCLC, including ongoing trials. Thus, we are providing an overview of what lies ahead in the field of epigenetic combinatory therapies of NSCLC in the coming years.
authors.affiliation: a Division of Hematology, Oncology and Stem Cell Transplantation , University of Freiburg, Medical Center , Freiburg , Germany.|b University of Freiburg, Faculty of Medicine , Freiburg , Germany.
authors.forename: Insa
authors.initials: I
authors.lastname: Schiffmann
authors.affiliation: a Division of Hematology, Oncology and Stem Cell Transplantation , University of Freiburg, Medical Center , Freiburg , Germany.|c University of Freiburg, Faculty of Biology , Freiburg , Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Greve
authors.affiliation: d University of Freiburg, Institute of Pharmaceutical Sciences , Freiburg , Germany.|e German Cancer Consortium (DKTK) , Freiburg , Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
authors.affiliation: a Division of Hematology, Oncology and Stem Cell Transplantation , University of Freiburg, Medical Center , Freiburg , Germany.|b University of Freiburg, Faculty of Medicine , Freiburg , Germany.|e German Cancer Consortium (DKTK) , Freiburg , Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000628:therapy*; D003131:Combined Modality Therapy; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy
chemical_list: D056572:Histone Deacetylase Inhibitors; D015254:DNA Modification Methylases
keywords: Chromatin; DNA methylation; DNMT; LSD1; NSCLC; epigenetics; histone modifications; lung cancer