Ibrutinib Exerts Potent Antifibrotic and Antitumor Activities in Mouse Models of Pancreatic Adenocarcinoma
Ibrutinib Exerts Potent Antifibrotic and Antitumor Activities in Mouse Models of Pancreatic Adenocarcinoma
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DOI：
10.1158/0008-5472.can-14-2852
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发表时间：
2015-04-15
期刊：
影响因子：
11.2
通讯作者：
Soucek, Laura
中科院分区：
文献类型：
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作者：
Masso-Valles, Daniel;Jauset, Toni;Soucek, Laura
胰腺导管腺癌（PDAC）的特征是致密的间质纤维炎症反应，这是有效治疗的主要障碍。促结缔组织增生基质包含许多炎性细胞，特别是作为PDAC微环境的关键组分的肥大细胞，并且这种浸润与不良的患者结果相关。事实上，已经假设基质消融对于改善PDAC患者的临床应答至关重要。伊布替尼是一种临床批准的布鲁顿酪氨酸激酶抑制剂，在β细胞肿瘤发生的小鼠模型中抑制肥大细胞和肿瘤进展。在这里，我们表明，伊曲替尼是非常有效的限制PDAC在转基因小鼠和患者来源的异种移植模型的疾病的生长。在这些不同的实验环境中，伊布替尼有效地减少了纤维化，延长了生存期，并改善了对临床标准治疗的反应。我们的研究结果提供了一个临床前的理由，立即评估的PDAC患者的临床疗效的伊曲替尼。（C）2015年AACR。
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 beta-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. (C)2015 AACR.