Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas.
Neuro Oncol
; 26(6): 1012-1024, 2024 Jun 03.
Article
en En
| MEDLINE
| ID: mdl-38285162
ABSTRACT
A majority of cancers (~85%) activate the enzyme telomerase to maintain telomere length over multiple rounds of cellular division. Telomerase-negative cancers activate a distinct, telomerase-independent mechanism of telomere maintenance termed alternative lengthening of telomeres (ALT). ALT uses homologous recombination to maintain telomere length and exhibits features of break-induced DNA replication. In malignant gliomas, the activation of either telomerase or ALT is nearly ubiquitous in pediatric and adult tumors, and the frequency with which these distinct telomere maintenance mechanisms (TMMs) is activated varies according to genetically defined glioma subtypes. In this review, we summarize the current state of the field of TMMs and their relevance to glioma biology and therapy. We review the genetic alterations and molecular mechanisms leading to telomerase activation or ALT induction in pediatric and adult gliomas. With this background, we review emerging evidence on strategies for targeting TMMs for glioma therapy. Finally, we comment on critical gaps and issues for moving the field forward to translate our improved understanding of glioma telomere maintenance into better therapeutic strategies for patients.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Telómero
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Telomerasa
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Homeostasis del Telómero
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Glioma
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
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Animals
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Child
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article