2013, Volume 7, Issue 4
Frontiers of Medicine >> 2013, Volume 7, Issue 4 doi: 10.1007/s11684-013-0293-z
Telomeric impact of conventional chemotherapy
1. Ruijin Hospital Af?liated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
2. Institut for Research on Cancer ??and Aging, Nice (IRCAN), Nice University, CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France;
3. Geriatric Unit, Cimiez ?Hospital, CHU of Nice, France; 4. Department of Medical Genetics, Archet 2 Hospital, CHU of Nice, France
Next Previous
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
京公网安备 11010502051620号
