DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

Author(s)

de Sousa, Juliana Ferreira ^[1] ; Serafim, Rodolfo Bortolozo ^[2] ; de Freitas, Laura Marise ^[3] ; Fontana, Carla Raquel ^[4] ; Valente, Valeria ^{[2, 4, 5]}

Affiliation

^[1] NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 - USA

^[2] Univ Sao Paulo, Dept Biol Celular & Mol & Bioagentes Patogen, Fac Med Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, SP - Brazil

^[4] Univ Estadual Paulista, Fac Ciencias Fatmaceut, Dept Anal Clin, UNESP, Rodovia Araraquara Jau, Km 01, BR-14800901 Araraquara, SP - Brazil

^[5] Ctr Terapia Celular CEPID FAPESP, Ribeirao Preto, SP - Brazil

• Document type: Review article
• Source: GENETICS AND MOLECULAR BIOLOGY; v. 43, n. 1, 1 2020.
• Web of Science Citations: 0

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)

• FAPESP's process: 16/05345-4 - Improving antimicrobial photodynamic therapy for infectious disease associating peptide aurein 1.2
• Grantee: Carla Raquel Fontana
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/13465-1 - Functional characterization of HJURP (Holliday junction recognizing protein) in glioblastoma multiforme cells
• Grantee: Valeria Valente
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/24581-5 - Evaluation of the role of photodynamic therapy combined with antimicrobial peptides against bacterial resistance
• Grantee: Laura Marise de Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/05018-9 - Investigation of HJURP action (Holliday Junction Recognizing Protein) in DNA repair activity of glioblastoma cells
• Grantee: Valeria Valente
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC