Data/hora: 10/06/2024 05:32:33

Provedor de dados: | Genetics and Molecular Biology
País: | Brazil
Título: | DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
Autores: | Sousa,Juliana Ferreira de; Serafim,Rodolfo Bortolozo; Freitas,Laura Marise de; Fontana,Carla Raquel; Valente,Valeria.
Data: | 2020-01-01
Ano: | 2020
Palavras-chave: | Glioblastoma; DNA repair; Biomarkers; Tumor progression; Therapy resistance.
Resumo: | Abstract Glioblastoma (GBM) is the most common and malignant type of primary brain tumor, showing rapid development and resistance to therapies. On average, patients survive 14.6 months after diagnosis and less than 5% survive five years or more. Several pieces of evidence have suggested that the DNA damage signaling and repair activities are directly correlated with GBM phenotype and exhibit opposite functions in cancer establishment and progression. The functions of these pathways appear to present a dual role in tumorigenesis and cancer progression. Activation and/or overexpression of ATRX, ATM and RAD51 genes were extensively characterized as barriers for GBM initiation, but paradoxically the exacerbated activity of these genes was further associated with cancer progression to more aggressive stages. Excessive amounts of other DNA repair proteins, namely HJURP, EXO1, NEIL3, BRCA2, and BRIP, have also been connected to proliferative competence, resistance and poor prognosis. This scenario suggests that these networks help tumor cells to manage replicative stress and treatment-induced damage, diminishing genome instability and conferring therapy resistance. Finally, in this review we address promising new drugs and therapeutic approaches with potential to improve patient survival. However, despite all technological advances, the prognosis is still dismal and further research is needed to dissect such complex mechanisms.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000200306
Editor: | Sociedade Brasileira de Genética
Relação: | 10.1590/1678-4685-gmb-2019-0066
Formato: | text/html
Fonte: | Genetics and Molecular Biology  v.43 n.1 suppl.1 2020
Fonte: | info:eu-repo/semantics/openAccess