Authors: Beeharry, N.; Broccoli, D.

Source: Current Molecular Medicine, Volume 5, Number 2, March 2005 , pp. 187-196(10)

Publisher: Bentham Science Publishers

Abstract:

The use of chemotherapy provides an essential arm in the treatment of a number of cancers. The biological feature common to all cancerous cells that sensitizes them to chemotherapeutic agents is their elevated division rate. Rapidly dividing cells, such as tumor cells, are more sensitive to chemotherapeutic agents that act to initiate pathways leading to cell death, a process enhanced in cells with compromised DNA damage responses. The toxicity accompanying chemotherapy is due to side-effects induced in normal regenerative tissues which also have relatively high replication rates, such as hair follicles, the hematopoietic system, the gastrointestinal system, the germline and skin cells. While the side-effects of chemotherapy may be tolerated by the patient, the long term impact of the cytotoxic effects of chemotherapy on healthy tissues is only now becoming apparent. Chemotherapy-induced cytotoxicity in regenerative tissues requires multiple cell divisions in order to reconstitute the affected tissues. At least in part as a consequence of these extra divisions, telomeres in individuals treated with chemotherapy are shorter than age-matched control individuals who have never been exposed to these drugs. Given the essential role of telomeres in regulating cellular aging and chromosomal stability, it is possible that the prematurely shortened telomeres that arise following chemotherapy may impact the long-term replicative potential of these tissues. This review is focused on how telomeres may be modulated, directly or indirectly, by anticancer drugs and the potential long-term consequences of accelerated telomere shortening in healthy tissue as a result of current cancer treatment protocols.

Keywords: anticancer drugs; apoptosis; signaling pathways; radiation therapy; chemotherapeutics; leukemia; hematopoietic system; telomeric dna

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1566524053586554

Affiliations: 1: Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.

Publication date: 2005-03-01

More about this publication?

• Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.

Related content

• In this: publication
• By this: publisher
• In this Subject: Pathology
• By this author: Beeharry, N. ;  Broccoli, D.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers