Brain perfusion and permeability in patients with advanced, refractory glioblastoma treated with lomustine and the transforming growth factor‑β receptor I kinase inhibitor LY2157299 monohydrate

Sepulveda‑Sanchez,Juan; Ramos,Ana; Hilario,Amaya; De Velasco,Guillermo; Castellano,Daniel; Garcia De La Torre,Marta; Rodon,Jordi; Lahn,Michael   F.

doi:10.3892/ol.2015.3106

Brain perfusion and permeability in patients with advanced, refractory glioblastoma treated with lomustine and the transforming growth factor‑β receptor I kinase inhibitor LY2157299 monohydrate

Authors:
- Juan Sepulveda‑Sanchez
- Ana Ramos
- Amaya Hilario
- Guillermo De Velasco
- Daniel Castellano
- Marta Garcia De La Torre
- Jordi Rodon
- Michael F. Lahn
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Affiliations: Department of Medical Oncology, University Hospital October 12, Madrid 28041, Spain, Department of Neuroradiology, University Hospital October 12, Madrid 28041, Spain, Eli Lilly and Company, Indianapolis, IN 46285, USA, Department of Medical Oncology, Vall d'Hebron University Hospital and The Autonomous University of Barcelona, Barcelona 08999, Spain
Published online on: April 8, 2015 https://doi.org/10.3892/ol.2015.3106
Pages: 2442-2448
Copyright: © Sepulveda‑Sanchez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transforming growth factor‑β (TGF‑β) signaling is associated with tumor progression and vascularization in malignant glioma. In the present study, magnetic resonance imaging was used to evaluate changes in the size and vascularity of glioblastomas in 12 patients who were treated with lomustine and the novel inhibitor of TGF‑β signaling, LY2157299 monohydrate. A response in tumor size was observed in 2 of the 12 patients; in 1 of these 2 patients, a reduction in vascular permeability and perfusion was also detected. The effect was observed following 4 cycles of treatment (~3 months). Changes in vascularity have not previously been attributed to treatment with lomustine; therefore, the effect may be associated with LY2157299 treatment. LY2157299 does not appear to have an anti‑angiogenic effect when combined with lomustine, and hence may have a different mechanism of action profile compared with anti‑angiogenic drugs.

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