title: Lung cancer stem cells: The root of resistance.
abstract: In the absence of specific treatable mutations, platinum-based chemotherapy remains the gold standard of treatment for lung cancer patients. However, 5-year survival rates remain poor due to the development of resistance and eventual relapse. Resistance to conventional cytotoxic therapies presents a significant clinical challenge in the treatment of this disease. The cancer stem cell (CSC) hypothesis suggests that tumors are arranged in a hierarchical structure, with the presence of a small subset of stem-like cells that are responsible for tumor initiation and growth. This CSC population has a number of key properties such as the ability to asymmetrically divide, differentiate and self-renew, in addition to having increased intrinsic resistance to therapy. While cytotoxic chemotherapy kills the bulk of tumor cells, CSCs are spared and have the ability to recapitulate the heterogenic tumor mass. The identification of lung CSCs and their role in tumor biology and treatment resistance may lead to innovative targeted therapies that may ultimately improve clinical outcomes in lung cancer patients. This review will focus on lung CSC markers, their role in resistance and their relevance as targets for future therapies.
authors.affiliation: Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Ireland.
authors.forename: Lauren
authors.initials: L
authors.lastname: MacDonagh
authors.affiliation: Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Ireland.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Gray
authors.affiliation: Flow Cytometry Core Facility, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Ireland.
authors.forename: Eamon
authors.initials: E
authors.lastname: Breen
authors.affiliation: Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Ireland.
authors.forename: Sinead
authors.initials: S
authors.lastname: Cuffe
authors.affiliation: Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Ireland; Department of Histopathology, St. James's Hospital and Trinity College Dublin, Ireland.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Finn
authors.affiliation: Cancer & Ageing Research Program, Queensland University of Technology, Brisbane, Australia.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
authors.affiliation: Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Ireland. Electronic address: mbarr@stjames.ie.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Barr
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D058985:Side-Population Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: Cancer stem cells; Chemotherapy; Lung cancer; Markers; Resistance