title: Targeting a cornerstone of radiation resistance: cancer stem cell.
abstract: In radiation oncology, cancer stem cells (CSCs) have become an important research field. In fact, it appears that most cancer types contain populations of cells that exhibit stem-cell properties. CSCs have the ability to renew indefinitely, which can drive tumor development and metastatic invasion. As those cells are classically resistant to conventional chemotherapy and to radiation therapy, they may contribute to treatment failure and relapse. Over past decades, preclinical research has highlighted that variations in the CSCs content within tumor could affect their radiocurability by interfering with mechanisms of DNA repair, redistribution in the cell cycle, tumor cells repopulation, and hypoxia. It is now possible to isolate particular cells expressing specific surface markers and thus better investigating CSCs pathways. Numerous inhibitory agents targeting these specific signaling pathways, such as Notch and Wnt/B-catenin, are currently evaluated in early clinical trials. By targeting CSCs, tumor radioresistance could be potentially overcome to improve outcome for patients with solid malignancies. Radiation therapy using ion particles (proton and carbon) may be also more effective than classic photon on CSCs. This review presents the major pathophysiological mechanisms involved in CSCs radioresistance and recent developments for targeted strategies.
authors.affiliation: Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Université de Lyon, Oullins, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Moncharmont
authors.forename: Antonin
authors.initials: A
authors.lastname: Levy
authors.forename: Marion
authors.initials: M
authors.lastname: Gilormini
authors.forename: Gérald
authors.initials: G
authors.lastname: Bertrand
authors.forename: Cyrus
authors.initials: C
authors.lastname: Chargari
authors.forename: Gersende
authors.initials: G
authors.lastname: Alphonse
authors.forename: Dominique
authors.initials: D
authors.lastname: Ardail
authors.forename: Claire
authors.initials: C
authors.lastname: Rodriguez-Lafrasse
authors.forename: Nicolas
authors.initials: N
authors.lastname: Magné
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000528:radiation effects*; D011836:Radiation Tolerance; D015398:Signal Transduction