Therapeutic targeting of c-Myc in T-cell acute lymphoblastic leukemia, T-ALL.
Oncotarget
; 5(10): 3168-72, 2014 May 30.
Article
en En
| MEDLINE
| ID: mdl-24930440
T-ALL patients treated with intensive chemotherapy achieve high rates of remission. However, frequent long-term toxicities and relapses into chemotherapy-refractory tumors constitute major clinical challenges which could be met by targeted therapies. c-MYC is a central oncogene in T-ALL, prompting the exploration of the efficacy of MYC inhibitors such as JQ1 (BET-bromodomain inhibitor), and SAHA (HDAC inhibitor). Using a standardized ex vivo drug screening assay, we show here that JQ1 and SAHA show competitive efficiency compared to inhibitors of proteasome, PI3K/AKT/mTOR and NOTCH pathways, and synergize in combination with Vincristine. We also compared for the first time the in vivo relevance of such associations in mice xenografted with human primary T-ALLs. Our data indicate that although treatments combining JQ1 or SAHA with chemotherapeutic regimens might represent promising developments in T-ALL, combinations will need to be tailored to specific subgroups of responsive patients, the profiles of which still remain to be precisely defined.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Proteínas Proto-Oncogénicas c-myc
/
Leucemia-Linfoma Linfoblástico de Células T Precursoras
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Oncotarget
Año:
2014
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos