title: Radiation resistance: Cancer stem cells (CSCs) and their enigmatic pro-survival signaling.
abstract: Despite the fact that radiation therapy is a highly effective therapeutic approach, a small intratumoral cell subpopulation known as "cancer stem cells" (CSCs) is radiation-resistant and possesses specific molecular properties protecting it against radiation-induced damage. The exact mechanisms of this radioresistance are still not fully elucidated, but they relate to these cells' enhanced DNA repair capacities and their low intracellular ROS concentrations, resulting from their up-regulation of ROS scavengers. The low ROS content is accompanied by disturbances in cell cycle regulation, so it can be assumed that either CSCs are quiescent or dormant themselves, or that this cell population consists of at least two cell subpopulations: the normally and the slowly proliferating cells (quiescent or dormant cells). Slowly dividing CSCs show concomitant dysregulation of the signaling molecules mediating both cell cycle progression and maintenance of cell stemness. Despite a massive accumulation of data concerning the mechanisms underlying DNA damage response in CSCs, it represents a challenge to researchers in the era of personalized medicine to elucidate the role of intracellular ROS and of signaling pathways associated with the radiation resistance of these cells; there is a clear need to understand the molecular mechanisms helping CSCs to survive radiation exposure.
authors.affiliation: Department of Therapeutic Radiology and Oncology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Ira.Skvortsova@i-med.ac.at.
authors.forename: Ira
authors.initials: I
authors.lastname: Skvortsova
authors.affiliation: Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Debbage
authors.affiliation: Centre for Chemical and Pharmaceutical Sciences, Central University of Punjab, Bathinda, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Therapeutic Radiology and Oncology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Sergej
authors.initials: S
authors.lastname: Skvortsov
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000528:radiation effects; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: Cancer stem cells; DNA repair; Dormancy; ROS; ROS scavengers; Radiation resistance