title: The role of telomeres in predicting individual radiosensitivity of patients with cancer in the era of personalized radiotherapy.
abstract: Radiotherapy plays a key role in cancer treatments, but tumor cell death differs from one tumor to another. The response of patients to radiotherapy varies considerably and adverse side effects are difficult to prevent. The mechanisms involved in the heterogeneity of this response are not well understood. In order to enhance the efficacy and safety of radiotherapy, it is important to identify subpopulations most at risk of developing a late adverse response to radiotherapy. Telomeres are composed of multiple repeats of a unique sequence of nucleotides forming a TTAGGG pattern. They protect chromosomes from end-to-end fusion and maintain genomic stability. Telomeres have been shown to be extremely sensitive to radiotherapy especially because of their atypical DNA damage repair response, which includes partial inhibition of the non-homologous end joining repair pathway. Ionizing Radiation (IR)-induced damage to telomere DNA could lead to chromosome instability and the initiation or progression of tumor processes. Telomeres could thus be a reliable marker of IR exposure and as such become a new parameter for predicting radiosensitivity. Furthermore, short telomeres are more sensitive to radiotherapy, which could partially explain differences in tumor cell death and in inter-individual sensitivity to radiotherapy. Telomere length could be used to identify subpopulations of patients who could benefit from higher or lower doses per fraction. Finally, pharmacological interference with tumor-cell telomere biology to reduce telomere length and/or telomere stability could also enhance the effectiveness and safety of radiotherapy. Telomeres could play a key role in radiotherapy in the era of personalized medicine.
authors.affiliation: Department of Radiation Oncology, Centre Georges-François Leclerc, Dijon, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Mirjolet
authors.affiliation: Department of Biology and Pathology of Tumors, Centre Georges-François Leclerc, Dijon, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Boidot
authors.affiliation: Department of Radiation Oncology, Centre Georges-François Leclerc, Dijon, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Saliques
authors.affiliation: Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France; INSERM Avenir U866, University of Burgundy, Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.affiliation: Department of Radiation Oncology, Centre Georges-François Leclerc, Dijon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maingon
authors.affiliation: Department of Radiation Oncology, Centre Georges-François Leclerc, Dijon, France. Electronic address: gcrehange@cgfl.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Créhange
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D057285:Precision Medicine / Q000379:methods*; D011237:Predictive Value of Tests; D011836:Radiation Tolerance / Q000235:genetics; D016615:Telomere / Q000235:genetics* / Q000378:metabolism
keywords: Chromosome instability; Ionizing radiations; Personalized medicine; Radiobiology; Telomerase; Telomere