Telomeric impact of conventional chemotherapy

Abstract

The increased level of chromosome instability in cancer cells, leading to aneuploidy and gross chromosomal rearrangements, is not only a driving force for oncogenesis but also can be the Achille’s heel of the disease since many chemotherapies (CT) kill cells by inducing a non-tolerable rate of DNA damage. A wealth of published evidence showed that telomere stability can be more affected than the bulk of the genome by several conventional antineoplasic drugs. These results raise the interesting possibility that CT with genotoxic drugs preferentially target telomeres. In agreement with this view, accelerated shortening of telomere length has been described in blood lineage cells following high-dose CT (stem cell transplantation) or non-myeloablative CT. However, almost nothing is known on the consequences of this shortening in terms of telomere stability, senescence and on the development of second cancers or post-treatment aging-like syndromes in cancer survivors (cognitive defect, fertility impairment, etc.). In this article, we propose: (1) telomeres of cancer cells are preferential genomic targets of chemotherapies altering chromosome maintenance; (2) telomere functional parameters can be a surrogate marker of chemotherapy sensitivity and toxicity; (3) the use of anti-telomere molecule could greatly enhance the sensitivity to standards chemotherapies.

Keywords

telomere / antineoplasic drugs / conventional chemotherapies

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Acknowledgements

The work in the JY lab is supported by National Natural Science Foundation of China (Grant Nos. 81270433, 81171846, and 81000875), Foundation for Young Scientist in Shanghai Municipal Health Bureau in China (Grant No.2010.24); Foundation for City Star of Science and Technology in Shanghai (Grant No. 11QA1404400).The work in the EG lab is supported by La Ligue Nationale Contre le Cancer (Équipe labélisée), l’Institut Nationale du Cancer (INCa, TELOFUN program), L’Agence Nationale de la Recherche (ANR, TELOREP program).

Compliance with ethics guidelines

Yiming Lu, Olivier Guérin, Eric Gilson, and Jing Ye declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg