The cancer-aging interface and the significance of telomere dynamics in cancer therapy.
The efficacy of most cancer treatments depends markedly on the high replication rate of cancer cells, a characteristic frequently observed in neoplasms with higher grades of malignancy. Yet, the same characteristic is present in many normal regenerative tissues of the body, which makes them susceptible to the cytotoxic effects of chemotherapeutics and accounts for many of the toxic side effects of these drugs. In response to cell killing by chemotherapeutics, normal regenerative tissues replicate at a faster rate to regenerate, resulting in accelerated telomere attrition and leaving different cell populations with telomeres shorter than they would normally have in the absence of treatment. This accelerated erosion has implications regarding the recurrence of cancers at secondary sites because reduced replicative ability may compromise effective subsequent immune responses. In this review we discuss recent reports describing the effect of chemotherapeutics on telomere loss, how this may impact healthy tissues in an age-dependent manner, and describe in brief emerging cancer treatments that may avoid this telomere erosion effect.
Tallen
Gesche
G
Department of Pediatric Oncology and Haematology, Charité, Universitätsmedizin-Berlin, Campus Virchow, Berlin, Germany.
Soliman
Mohamed A
MA
Riabowol
Karl
K
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007107:Immune System; D007223:Infant; D007231:Infant, Newborn; D008017:Life Expectancy; D008136:Longevity; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D016615:Telomere / Q000648:ultrastructure*