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

Pierre Jean Le Reste; Raphael Pineau; Konstantinos Voutetakis; Juhi Samal; Gwénaële Jégou; Stéphanie Lhomond; Adrienne M Gorman; Afshin Samali; John B Patterson; Qingping Zeng; Abhay Pandit; Marc Aubry; Nicolas Soriano; Amandine Etcheverry; Aristotelis Chatziioannou; Jean Mosser; Tony Avril; Eric Chevet

doi:10.1016/j.canlet.2020.08.028

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

Pierre Jean Le Reste, Raphael Pineau, Konstantinos Voutetakis, Juhi Samal, Gwénaële Jégou, Stéphanie Lhomond, Adrienne M Gorman, Afshin Samali, John B Patterson, Qingping Zeng, Abhay Pandit, Marc Aubry, Nicolas Soriano, Amandine Etcheverry, Aristotelis Chatziioannou, Jean Mosser, Tony Avril, Eric Chevet

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

Abstract

Glioblastoma multiforme (GBM) is the most severe primary brain cancer. Despite an aggressive treatment comprising surgical resection and radio/chemotherapy, patient's 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
Pages (from-to)	73-83
Number of pages	11
Journal	Cancer Letters
Volume	494
DOIs	https://doi.org/10.1016/j.canlet.2020.08.028
Publication status	Published - 1 Dec 2020

Keywords

Animals
Benzopyrans/administration & dosage
Brain Neoplasms/genetics
Cell Line, Tumor
Combined Modality Therapy/methods
Craniotomy
Drug Therapy
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glioblastoma/genetics
Humans
Immunocompetence
Injections, Intralesional
Mice
Morpholines/administration & dosage
Neoadjuvant Therapy
Radiotherapy
Treatment Outcome
Tumor Microenvironment/drug effects
Xenograft Model Antitumor Assays

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2020.08.028

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Le Reste, P. J., Pineau, R., Voutetakis, K., Samal, J., Jégou, G., Lhomond, S., Gorman, A. M., Samali, A., Patterson, J. B., Zeng, Q., Pandit, A., Aubry, M., Soriano, N., Etcheverry, A., Chatziioannou, A., Mosser, J., Avril, T., & Chevet, E. (2020). Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation/chemotherapy in vivo. Cancer Letters, 494, 73-83. https://doi.org/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, patient's 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.",

keywords = "Animals, Benzopyrans/administration \& dosage, Brain Neoplasms/genetics, Cell Line, Tumor, Combined Modality Therapy/methods, Craniotomy, Drug Therapy, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glioblastoma/genetics, Humans, Immunocompetence, Injections, Intralesional, Mice, Morpholines/administration \& dosage, Neoadjuvant Therapy, Radiotherapy, Treatment Outcome, Tumor Microenvironment/drug effects, Xenograft Model Antitumor Assays",

author = "\{Le Reste\}, \{Pierre Jean\} and Raphael Pineau and Konstantinos Voutetakis and Juhi Samal and Gw{\'e}na{\"e}le J{\'e}gou and St{\'e}phanie Lhomond and Gorman, \{Adrienne M\} and Afshin Samali and Patterson, \{John B\} and Qingping Zeng and Abhay Pandit and Marc Aubry and Nicolas Soriano and Amandine Etcheverry and Aristotelis Chatziioannou and Jean Mosser and Tony Avril and Eric Chevet",

year = "2020",

month = dec,

day = "1",

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

language = "English",

volume = "494",

pages = "73--83",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

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Le Reste, PJ, Pineau, R, Voutetakis, K, Samal, J, Jégou, G, Lhomond, S, Gorman, AM , Samali, A, Patterson, JB, Zeng, Q, Pandit, A, Aubry, M, Soriano, N, Etcheverry, A, Chatziioannou, A, Mosser, J, Avril, T & Chevet, E 2020, 'Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation/chemotherapy in vivo', Cancer Letters, vol. 494, pp. 73-83. https://doi.org/10.1016/j.canlet.2020.08.028

TY - JOUR

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

AU - Le Reste, Pierre Jean

AU - Pineau, Raphael

AU - Voutetakis, Konstantinos

AU - Samal, Juhi

AU - Jégou, Gwénaële

AU - Lhomond, Stéphanie

AU - Gorman, Adrienne M

AU - Samali, Afshin

AU - Patterson, John B

AU - Zeng, Qingping

AU - Pandit, Abhay

AU - Aubry, Marc

AU - Soriano, Nicolas

AU - Etcheverry, Amandine

AU - Chatziioannou, Aristotelis

AU - Mosser, Jean

AU - Avril, Tony

AU - Chevet, Eric

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, patient's 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, patient's 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 - Animals

KW - Benzopyrans/administration & dosage

KW - Brain Neoplasms/genetics

KW - Cell Line, Tumor

KW - Combined Modality Therapy/methods

KW - Craniotomy

KW - Drug Therapy

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Glioblastoma/genetics

KW - Humans

KW - Immunocompetence

KW - Injections, Intralesional

KW - Mice

KW - Morpholines/administration & dosage

KW - Neoadjuvant Therapy

KW - Radiotherapy

KW - Treatment Outcome

KW - Tumor Microenvironment/drug effects

KW - Xenograft Model Antitumor Assays

U2 - 10.1016/j.canlet.2020.08.028

DO - 10.1016/j.canlet.2020.08.028

M3 - Article

C2 - 32882336

SN - 0304-3835

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

UN SDGs

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