title: DNA repair mechanisms and their clinical impact in glioblastoma.
abstract: Despite surgical resection and genotoxic treatment with ionizing radiation and the DNA alkylating agent temozolomide, glioblastoma remains one of the most lethal cancers, due in great part to the action of DNA repair mechanisms that drive resistance and tumor relapse. Understanding the molecular details of these mechanisms and identifying potential pharmacological targets have emerged as vital tasks to improve treatment. In this review, we introduce the various cellular systems and animal models that are used in studies of DNA repair in glioblastoma. We summarize recent progress in our knowledge of the pathways and factors involved in the removal of DNA lesions induced by ionizing radiation and temozolomide. We introduce the therapeutic strategies relying on DNA repair inhibitors that are currently being tested in vitro or in clinical trials, and present the challenges raised by drug delivery across the blood brain barrier as well as new opportunities in this field. Finally, we review the genetic and epigenetic alterations that help shape the DNA repair makeup of glioblastoma cells, and discuss their potential therapeutic impact and implications for personalized therapy.
authors.affiliation: NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg.
authors.forename: Hélène
authors.initials: H
authors.lastname: Erasimus
authors.affiliation: NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Gobin
authors.affiliation: NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg.
authors.forename: Simone
authors.initials: S
authors.lastname: Niclou
authors.affiliation: NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg. Electronic address: eric.vandyck@lih.lu.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Dyck
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D011878:Radiotherapy; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers
keywords: Chemoresistance; DNA repair; Glioblastoma; Ionizing radiation; Temozolomide; Therapeutic strategies