Telomere maintenance as therapeutic target in embryonal tumours.
Embryonal tumours most commonly occur in the first few years of life and account for approximately 30% of childhood malignancies. Knowledge of these tumours' genetics has already impacted on their clinical management and further knowledge of their cellular immortalization will hopefully result in novel therapies. The ends of human chromosomes are capped and protected by telomeres; cellular replication, however, causes their loss. A critical length of telomere repeats is required to ensure proper telomere function and avoid the activation of DNA damage pathways that result in senescence and cell death. To proliferate beyond the senescence checkpoint, cells must restore their telomere length. Hence stabilization of telomere is an important step in cell immortalization and carcinogenesis. Telomere maintenance is evident in virtually all types of malignant cells, including embryonal tumours, where either a telomerase-dependent or alternative lengthening of telomeres (ALT) mechanism is employed in order to ensure their limitless replicative potential. For this reason effective strategies targeting telomere maintenance in cancer cells require a combination of telomerase and ALT inhibitors. In this review, we are giving an overview about telomere maintenance in childhood tumours and discussing its potential as a new therapeutic target.
Shalaby
T
T
Neuro-Oncology Program, Department of Oncology, University Children's Hospital of Zurich, Switzerland.
Hiyama
E
E
Grotzer
M A
MA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D004622:Embryo, Mammalian / Q000201:enzymology; D054856:G-Quadruplexes / Q000187:drug effects; D018197:Hepatoblastoma / Q000235:genetics; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics; D051379:Mice; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000503:physiopathology; D009447:Neuroblastoma / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000235:genetics; D012512:Sarcoma, Ewing / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016615:Telomere / Q000187:drug effects / Q000378:metabolism*; D009396:Wilms Tumor / Q000235:genetics
D000970:Antineoplastic Agents; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse