DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

Detalhes bibliográficos
Autor(a) principal: Sousa,Juliana Ferreira de
Data de Publicação: 2020
Outros Autores: Serafim,Rodolfo Bortolozo, Freitas,Laura Marise de, Fontana,Carla Raquel, Valente,Valeria
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Genetics and Molecular Biology
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000200306
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.
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spelling DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistanceGlioblastomaDNA repairbiomarkerstumor progressiontherapy resistanceAbstract 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.Sociedade Brasileira de Genética2020-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000200306Genetics and Molecular Biology v.43 n.1 suppl.1 2020reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/1678-4685-gmb-2019-0066info:eu-repo/semantics/openAccessSousa,Juliana Ferreira deSerafim,Rodolfo BortolozoFreitas,Laura Marise deFontana,Carla RaquelValente,Valeriaeng2019-12-10T00:00:00Zoai:scielo:S1415-47572020000200306Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2019-12-10T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false
dc.title.none.fl_str_mv DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
title DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
spellingShingle DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
Sousa,Juliana Ferreira de
Glioblastoma
DNA repair
biomarkers
tumor progression
therapy resistance
title_short DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
title_full DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
title_fullStr DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
title_full_unstemmed DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
title_sort DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
author Sousa,Juliana Ferreira de
author_facet Sousa,Juliana Ferreira de
Serafim,Rodolfo Bortolozo
Freitas,Laura Marise de
Fontana,Carla Raquel
Valente,Valeria
author_role author
author2 Serafim,Rodolfo Bortolozo
Freitas,Laura Marise de
Fontana,Carla Raquel
Valente,Valeria
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Sousa,Juliana Ferreira de
Serafim,Rodolfo Bortolozo
Freitas,Laura Marise de
Fontana,Carla Raquel
Valente,Valeria
dc.subject.por.fl_str_mv Glioblastoma
DNA repair
biomarkers
tumor progression
therapy resistance
topic Glioblastoma
DNA repair
biomarkers
tumor progression
therapy resistance
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020-01-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000200306
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000200306
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/1678-4685-gmb-2019-0066
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Genética
publisher.none.fl_str_mv Sociedade Brasileira de Genética
dc.source.none.fl_str_mv Genetics and Molecular Biology v.43 n.1 suppl.1 2020
reponame:Genetics and Molecular Biology
instname:Sociedade Brasileira de Genética (SBG)
instacron:SBG
instname_str Sociedade Brasileira de Genética (SBG)
instacron_str SBG
institution SBG
reponame_str Genetics and Molecular Biology
collection Genetics and Molecular Biology
repository.name.fl_str_mv Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)
repository.mail.fl_str_mv ||editor@gmb.org.br
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