Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation chemotherapy in vivo

Adrienne Gorman; Afshin Samali

doi:10.1016/j.canlet.2020.08.028

Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation chemotherapy in vivo

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Abstract

Glioblastoma multiforme (GBM) is the most severe primary brain cancer. Despite an aggressive treatment comprising surgical resection and radio chemotherapy, patients survival post diagnosis remains short. A limitation for success in finding novel improved therapeutic options for such dismal disease partly lies in the lack of a relevant animal model that accurately recapitulates patient disease and standard of care. In the present study, we have developed an immunocompetent GBM model that includes tumor surgery and a radio chemotherapy regimen resembling the Stupp protocol and we have used this model to test the impact of the pharmacological inhibition of the endoplasmic reticulum (ER) stress sensor IRE1, on treatment efficacy.

Original language	English (Ireland)
Pages (from-to)	73-83
Number of pages	10
Journal	Cancer Letters
Volume	494
DOIs	https://doi.org/10.1016/j.canlet.2020.08.028
Publication status	Published - 1 Dec 2020

Keywords

Endoplasmic reticulum
Glioblastoma
IRE1
Unfolded Protein Response

Authors (Note for portal: view the doc link for the full list of authors)

Authors
Le Reste, PJ;Pineau, R;Voutetakis, K;Samal, J;Jegou, G;Lhomond, S;Gorman, AM;Samali, A;Patterson, JB;Zeng, QP;Pandit, A;Aubry, M;Soriano, N;Etcheverry, A;Chatziioannou, A;Mosser, J;Avril, T;Chevet, E

UN SDGs

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10.1016/j.canlet.2020.08.028

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title = "Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation chemotherapy in vivo",

abstract = "Glioblastoma multiforme (GBM) is the most severe primary brain cancer. Despite an aggressive treatment comprising surgical resection and radio chemotherapy, patients survival post diagnosis remains short. A limitation for success in finding novel improved therapeutic options for such dismal disease partly lies in the lack of a relevant animal model that accurately recapitulates patient disease and standard of care. In the present study, we have developed an immunocompetent GBM model that includes tumor surgery and a radio chemotherapy regimen resembling the Stupp protocol and we have used this model to test the impact of the pharmacological inhibition of the endoplasmic reticulum (ER) stress sensor IRE1, on treatment efficacy.",

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author = "Adrienne Gorman and Afshin Samali",

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year = "2020",

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doi = "10.1016/j.canlet.2020.08.028",

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T1 - Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation chemotherapy in vivo

AU - Gorman, Adrienne

AU - Samali, Afshin

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Glioblastoma multiforme (GBM) is the most severe primary brain cancer. Despite an aggressive treatment comprising surgical resection and radio chemotherapy, patients survival post diagnosis remains short. A limitation for success in finding novel improved therapeutic options for such dismal disease partly lies in the lack of a relevant animal model that accurately recapitulates patient disease and standard of care. In the present study, we have developed an immunocompetent GBM model that includes tumor surgery and a radio chemotherapy regimen resembling the Stupp protocol and we have used this model to test the impact of the pharmacological inhibition of the endoplasmic reticulum (ER) stress sensor IRE1, on treatment efficacy.

AB - Glioblastoma multiforme (GBM) is the most severe primary brain cancer. Despite an aggressive treatment comprising surgical resection and radio chemotherapy, patients survival post diagnosis remains short. A limitation for success in finding novel improved therapeutic options for such dismal disease partly lies in the lack of a relevant animal model that accurately recapitulates patient disease and standard of care. In the present study, we have developed an immunocompetent GBM model that includes tumor surgery and a radio chemotherapy regimen resembling the Stupp protocol and we have used this model to test the impact of the pharmacological inhibition of the endoplasmic reticulum (ER) stress sensor IRE1, on treatment efficacy.

KW - Endoplasmic reticulum

KW - Glioblastoma

KW - IRE1

KW - Unfolded Protein Response

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U2 - 10.1016/j.canlet.2020.08.028

DO - 10.1016/j.canlet.2020.08.028

M3 - Article

VL - 494

SP - 73

EP - 83

JO - Cancer Letters

JF - Cancer Letters

ER -

Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation chemotherapy in vivo

Abstract

Keywords

Authors (Note for portal: view the doc link for the full list of authors)

UN SDGs

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