Reference Detail

Ref Type Journal Article
PMID (26206868)
Authors Bill R, Fagiani E, Zumsteg A, Antoniadis H, Johansson D, Haefliger S, Albrecht I, Hilberg F, Christofori G
Title Nintedanib Is a Highly Effective Therapeutic for Neuroendocrine Carcinoma of the Pancreas (PNET) in the Rip1Tag2 Transgenic Mouse Model.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 21
Issue 21
Date 2015 Nov 01
URL
Abstract Text Pancreatic neuroendocrine tumors (PNET) represent a rare but challenging heterogeneous group of cancers with an increasing incidence over the last number of decades. Herein, we report an in-depth evaluation of the new antiangiogenic small-molecule tyrosine kinase inhibitor (TKI) nintedanib in the preclinical Rip1Tag2 transgenic mouse model of neuroendocrine carcinoma of the pancreas (insulinoma).We have assessed the antiangiogenic and antitumor activity of nintedanib, in comparison with other antiangiogenic TKI, by treating Rip1Tag2 transgenic mice with different treatment schedules complemented with histopathologic, cell biologic, and biochemical analyses.Prolonged nintedanib treatment of Rip1Tag2 mice has led to a strong suppression of angiogenesis, accompanied by a reduced tumor burden, which translated into a significant prolongation of survival. Despite nintedanib's inhibitory action on perivascular cells, the blood vessels remaining after therapy displayed a considerably mature phenotype with tight perivascular cell coverage and preserved perfusion. Nintedanib treatment did not increase local tumor invasiveness or metastasis to the liver and pancreatic lymph nodes--a phenomenon that has been observed with antiangiogenic treatments of Rip1Tag2 transgenic mice in other laboratories. In contrast with the strong reduction in blood microvessel densities, nintedanib did not have any impact on tumor lymphangiogenesis.Based on our findings, we propose the clinical evaluation of the antiangiogenic drug nintedanib as a new treatment modality for PNET patients, notably in a direct comparison with already established therapeutic regimens, such as sunitinib.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown pancreatic endocrine carcinoma not applicable Nintedanib Preclinical Actionable In a preclinical study, Ofev (nintedanib) induced tumor cell apoptosis, decreased microvessel density, inhibited tumor growth, and improved survival in transgenic mouse models of pancreatic neuroendocrine carcinoma (PMID: 26206868). 26206868