Ibrutinib exerts potent antifibrotic and antitumor activities in mouse models of pancreatic adenocarcinoma.

Autor:	Massó-Vallés D; Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, Barcelona, Spain., Jauset T; Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, Barcelona, Spain., Serrano E; Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, Barcelona, Spain., Sodir NM; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom., Pedersen K; Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, Barcelona, Spain., Affara NI; Department of Pathology, University of California, San Francisco, California., Whitfield JR; Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, Barcelona, Spain., Beaulieu ME; Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, Barcelona, Spain., Evan GI; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom. Department of Pathology, University of California, San Francisco, California., Elias L; Pharmacyclics Inc., Sunnyvale, California., Arribas J; Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain., Soucek L; Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. lsoucek@vhio.net.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2015 Apr 15; Vol. 75 (8), pp. 1675-81.
DOI:	10.1158/0008-5472.CAN-14-2852
Abstrakt:	Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stromal fibroinflammatory reaction that is a major obstacle to effective therapy. The desmoplastic stroma comprises many inflammatory cells, in particular mast cells as key components of the PDAC microenvironment, and such infiltration correlates with poor patient outcome. Indeed, it has been hypothesized that stromal ablation is critical to improve clinical response in patients with PDAC. Ibrutinib is a clinically approved Bruton's tyrosine kinase inhibitor that inhibits mast cells and tumor progression in a mouse model of β-cell tumorigenesis. Here, we show that ibrutinib is highly effective at limiting the growth of PDAC in both transgenic mouse and patient-derived xenograft models of the disease. In these various experimental settings, ibrutinib effectively diminished fibrosis, extended survival, and improved the response to clinical standard-of-care therapy. Our results offer a preclinical rationale to immediately evaluate the clinical efficacy of ibrutinib in patients with PDAC. (©2015 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu