DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

Autor(es)

Juliana Ferreira de Sousa ; Rodolfo Bortolozo Serafim ; Laura Marise de Freitas ; Carla Raquel Fontana ; Valeria Valente

• Tipo de documento: Artigo Científico
• Fonte: GENETICS AND MOLECULAR BIOLOGY; v. 43, n. 1, p. -, 2020.

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. (AU)

• Processo FAPESP: 14/24581-5 - Avaliação do papel da terapia fotodinâmica combinada a peptídeos antimicrobianos frente à resistência bacteriana
• Beneficiário: Laura Marise de Freitas
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/05345-4 - Otimização da terapia fotodinâmica para doenças infecciosas utilizando o peptídeo aureína 1.2
• Beneficiário: Carla Raquel Fontana Mendonça
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/13465-1 - Caracterização funcional da HJURP (Holliday junction recognizing protein) em células de glioblastoma multiforme
• Beneficiário: Valeria Valente
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/05018-9 - Investigação do mecanismo de ação da HJURP (Holliday Junction Recognizing Protein) no Reparo de DNA em células de glioblastoma
• Beneficiário: Valeria Valente
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs