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.