Miniatura

Fitxers

646621.pdf (1.11 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2014-07-25

Llicència de publicació

cc-by (c) Rosich, Laia et al., 2014
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/121170

Dual PI3K/mTOR inhibition is required to effectively impair microenvironment survival signals in mantle cell lymphoma

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.18632/oncotarget.2253

Resum

Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. Antitumor activity has been observed with mTOR inhibitors. However, they have shown limited clinical efficacy in relation to drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we have performed a comparative analysis of the mTOR inhibitor everolimus, the pan-PI3K inhibitor NVP-BKM120 and the dual PI3K/mTOR inhibitor NVP-BEZ235 in primary MCL cells. We found NVP-BEZ235 to be more powerful than everolimus or NVP-BKM120 in PI3K/Akt/mTOR signaling inhibition, indicating that targeting the PI3K/Akt/mTOR pathway at multiple levels is likely to be a more effective strategy for the treatment of MCL than single inhibition of these kinases. Among the three drugs, NVP-BEZ235 induced the highest change in gene expression profile. Functional validation demonstrated that NVP-BEZ235 inhibited angiogenesis, migration and tumor invasiveness in MCL cells. NVP-BEZ235 was the only drug able to block IL4 and IL6/STAT3 signaling which compromise the therapeutic effect of chemotherapy in MCL. Our findings support the use of the dual PI3K/mTOR inhibitor NVP-BEZ235 as a promising approach to interfere with the microenvironment-related processes in MCL.

Matèries

Cicle cel·lular, Limfomes, Càncer, Carcinogènesi, Citoquines

Matèries (anglès)

Cell cycle, Lymphomas, Cancer, Carcinogenesis, Cytokines

Citació

Col·leccions

Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

ROSICH, Laia, MONTRAVETA, Arnau, XARGAY I TORRENT, Sílvia, LÓPEZ-GUERRA, Mónica, ROLDÁN, Jocabed, AYMERICH GREGORIO, Marta, SALAVERRIA FRIGOLA, Itziar, BEÀ BOBET, Sílvia m., CAMPO GÜERRI, Elias, PÉREZ GALÁN, Patricia, ROUÉ, Gaël, COLOMER PUJOL, Dolors. Dual PI3K/mTOR inhibition is required to effectively impair microenvironment survival signals in mantle cell lymphoma. _Oncotarget_. 2014. Vol. 5, núm. 16, pàgs. 6788-6800. [consulta: 22 de gener de 2026]. ISSN: 1949-2553. [Disponible a: https://hdl.handle.net/2445/121170]

Exportar metadades

JSON - METS

Compartir registre