| Texto completo | |
| Autor(es): |
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
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BIOMEDICINES; v. 11, n. 4, p. 19-pg., 2023-04-01. |
| Resumo | |
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) | |
| Processo FAPESP: | 22/02200-6 - O papel da autofagia na resistência à quimioterápicos |
| Beneficiário: | Clarissa Ribeiro Reily Rocha |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 21/11597-4 - Análise do papel do gene NRF2 na modulação da ferroptose em linhagens tumorais resistentes a quimioterapia |
| Beneficiário: | Izadora de Souza |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 22/03130-1 - O papel das vias da autofagia e NRF2 na ferroptose |
| Beneficiário: | Clarissa Ribeiro Reily Rocha |
| Modalidade de apoio: | Auxílio à Pesquisa - Projeto Inicial |