DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , |
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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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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1752122389717581824 |