title: Determinants of resistance to chemotherapy and ionizing radiation in breast cancer stem cells.
abstract: Breast cancer cells are suggested to be organized in a hierarchical manner with a subpopulation of stem cells, termed as breast cancer stem cells (BCSCs), which contribute significantly to tumorigenesis, cancer recurrence and metastasis. BCSCs have been demonstrated to exhibit significant resistance to conventional chemo- and radiotherapy. Recent evidence suggests that treatment of breast cancers with radiation or chemotherapy agents induces stem cell-like properties in non-stem cells. Herein, we provide an overview of the key determinants of resistance to chemotherapy and radiation in BCSCs. To this end and by the use of bioinformatics, the molecular pathways, the defining markers, as well as the microenvironmental and genetic factors, which are implicated in the maintenance of stemness, chemo- and radioresistance in BCSCs, are identified and presented. Our findings could provide the foundation for the design of targeted chemo- or radiotherapeutic regimens in order to eliminate or sensitize BCSCs to cytotoxic therapies and prevent tumor relapse and metastasis.
authors.affiliation: Centre of Systems Biology, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efesiou, Athens 11527, Greece. Electronic address: apavlopoulou@bioacademy.gr.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Pavlopoulou
authors.affiliation: Izmir Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylül University, Izmir 35340, Turkey.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Oktay
authors.affiliation: Proteomics Research Unit, Center of Basic Research II, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efesiou, Athens 11527, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Vougas
authors.affiliation: Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Zografou Campus, Athens 15701, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Louka
authors.affiliation: Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Zografou Campus, Athens 15701, Greece.
authors.forename: Constantinos E
authors.initials: CE
authors.lastname: Vorgias
authors.affiliation: DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Iroon Polytechniou 9, Zografou 15780, Athens, Greece. Electronic address: alexg@mail.ntua.gr.
authors.forename: Alexandros G
authors.initials: AG
authors.lastname: Georgakilas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019295:Computational Biology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D053263:Gene Regulatory Networks; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D010641:Phenotype; D060066:Protein Interaction Maps; D011836:Radiation Tolerance / Q000235:genetics; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: Bioinformatics; Breast cancer stem cells; Chemoresistance; Chemotherapy; Radioresistance; Radiotherapy