| Full text | |
| Author(s): |
Lima, Karoline Almeida
;
Osawa, Isabeli Yumi Araujo
;
Ramalho, Maria Carolina Clares
;
de Souza, Izadora
;
Guedes, Camila Banca
;
de Souza Filho, Claudio Henrique Dahne
;
Monteiro, Linda Karolynne Seregni
;
Latancia, Marcela Teatin
;
Rocha, Clarissa Ribeiro Reily
Total Authors: 9
|
| Document type: | Journal article |
| Source: | BIOMEDICINES; v. 11, n. 4, p. 19-pg., 2023-04-01. |
| Abstract | |
The transcription factor NRF2 is constitutively active in glioblastoma, a highly aggressive brain tumor subtype with poor prognosis. Temozolomide (TMZ) is the primary chemotherapeutic agent for this type of tumor treatment, but resistance to this drug is often observed. This review highlights the research that is demonstrating how NRF2 hyperactivation creates an environment that favors the survival of malignant cells and protects against oxidative stress and TMZ. Mechanistically, NRF2 increases drug detoxification, autophagy, DNA repair, and decreases drug accumulation and apoptotic signaling. Our review also presents potential strategies for targeting NRF2 as an adjuvant therapy to overcome TMZ chemoresistance in glioblastoma. Specific molecular pathways, including MAPKs, GSK3 beta, beta TRCP, PI3K, AKT, and GBP, that modulate NRF2 expression leading to TMZ resistance are discussed, along with the importance of identifying NRF2 modulators to reverse TMZ resistance and develop new therapeutic targets. Despite the significant progress in understanding the role of NRF2 in GBM, there are still unanswered questions regarding its regulation and downstream effects. Future research should focus on elucidating the precise mechanisms by which NRF2 mediates resistance to TMZ, and identifying potential novel targets for therapeutic intervention. (AU) | |
| FAPESP's process: | 22/02200-6 - The role of autophagy in drug resistance |
| Grantee: | Clarissa Ribeiro Reily Rocha |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 21/11597-4 - Analysis of the role of NRF2 in ferroptosis modulation in chemotherapy-resistant tumor cell lines |
| Grantee: | Izadora de Souza |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 22/03130-1 - The role of autophagy and NRF2 pathways in ferroptosis |
| Grantee: | Clarissa Ribeiro Reily Rocha |
| Support Opportunities: | Research Grants - Initial Project |