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Targeting glioblastoma-derived pericytes improves chemotherapeutic outcome

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Abstract

Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood–brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood–brain barrier permeability, and prolonging survival. This study identifies glioblastoma-derived pericyte as a novel target in the brain tumor microenvironment during carcinogenesis. Here, we summarize and evaluate recent advances in the understanding of pericyte’s role in the glioblastoma microenvironment.

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Acknowledgements

Alexander Birbrair is supported by a grant from Instituto Serrapilheira/Serra-1708-15285, a Grant from Pró-reitoria de Pesquisa/Universidade Federal de Minas Gerais (PRPq/UFMG) (Edital 05/2016); a Grant from FAPEMIG [Rede Mineira de Engenharia de Tecidos e Terapia Celular (REMETTEC, RED-00570-16)], and a Grant from FAPEMIG [Rede De Pesquisa Em Doenças Infecciosas Humanas E Animais Do Estado De Minas Gerais (RED-00313-16)]; Akiva Mintz is supported by the National Institute of Health (1R01CA179072-01A1) and by the American Cancer Society Mentored Research Scholar Grant (124443-MRSG-13-121-01-CDD).

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  1. Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

    Daniel A. P. Guerra, Ana E. Paiva, Isadora F. G. Sena, Patrick O. Azevedo, Walison N. Silva & Alexander Birbrair

  2. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Akiva Mintz & Alexander Birbrair

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  1. Daniel A. P. Guerra
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  2. Ana E. Paiva
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  3. Isadora F. G. Sena
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Guerra, D.A.P., Paiva, A.E., Sena, I.F.G. et al. Targeting glioblastoma-derived pericytes improves chemotherapeutic outcome. Angiogenesis 21, 667–675 (2018). https://doi.org/10.1007/s10456-018-9621-x

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