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

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

doi:10.1016/j.canlet.2020.08.028

Cited by 42 publications

(26 citation statements)

References 26 publications

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“…The most common and aggressive malignancy in brain tumors is Glioblastoma Multiforme (GBM)( Duwa et al, 2019 ; Gong et al, 2019 ; Le Reste et al, 2020 ; Rahn et al, 2020 ). Currently, surgical resection, chemotherapy, and radiation therapy are mainly used for treatment, but the tumor often regrowth and the survival rate of GBM patients is low (Jeong et al, 2008 ; Floyd et al, 2015 ; Hotchkiss & Sampson, 2021 ).…”

Section: Applicationmentioning

confidence: 99%

PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application

Zhang²,

Sun³

et al. 2021

Drug Delivery

305

106

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Biodegradable microspheres have been widely used in the field of medicine due to their ability to deliver drug molecules of various properties through multiple pathways and their advantages of low dose and low side effects. Poly (lactic-co-glycolic acid) copolymer (PLGA) is one of the most widely used biodegradable material currently and has good biocompatibility. In application, PLGA with a specific monomer ratio (lactic acid and glycolic acid) can be selected according to the properties of drug molecules and the requirements of the drug release rate. PLGA-based biodegradable microspheres have been studied in the field of drug delivery, including the delivery of various anticancer drugs, protein or peptide drugs, bacterial or viral DNA, etc. This review describes the basic knowledge and current situation of PLGA biodegradable microspheres and discusses the selection of PLGA polymer materials. Then, the preparation methods of PLGA microspheres are introduced, including emulsification, microfluidic technology, electrospray, and spray drying. Finally, this review summarizes the application of PLGA microspheres in drug delivery and the treatment of pulmonary and ocularrelated diseases.

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Section: Applicationmentioning

confidence: 99%

PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application

Zhang²,

Sun³

et al. 2021

Drug Delivery

305

106

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“…As the inhibitor does not pass the BBB, it was delivered intraoperatively by means of a biomaterial scaffold. Such combined treatment significantly increased mouse survival (~20%) compared to the Stupp protocol alone and resulted in a completely different tumor phenotype [132]. Co-administration of MKC-8866 with another chemotherapeutic agent, paclitaxel, enhanced tumor suppression and delayed tumor relapse after therapy in a triple-negative breast cancer (TNBC) xenograft mouse model [133].…”

Section: Mkc Inhibitorsmentioning

confidence: 99%

The Structure, Activation and Signaling of IRE1 and Its Role in Determining Cell Fate

et al. 2021

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Inositol-requiring enzyme type 1 (IRE1) is a serine/threonine kinase acting as one of three branches of the Unfolded Protein Response (UPR) signaling pathway, which is activated upon endoplasmic reticulum (ER) stress conditions. It is known to be capable of inducing both pro-survival and pro-apoptotic cellular responses, which are strictly related to numerous human pathologies. Among others, IRE1 activity has been confirmed to be increased in cancer, neurodegeneration, inflammatory and metabolic disorders, which are associated with an accumulation of misfolded proteins within ER lumen and the resulting ER stress conditions. Emerging evidence suggests that genetic or pharmacological modulation of IRE1 may have a significant impact on cell viability, and thus may be a promising step forward towards development of novel therapeutic strategies. In this review, we extensively describe the structural analysis of IRE1 molecule, the molecular dynamics associated with IRE1 activation, and interconnection between it and the other branches of the UPR with regard to its potential use as a therapeutic target. Detailed knowledge of the molecular characteristics of the IRE1 protein and its activation may allow the design of specific kinase or RNase modulators that may act as drug candidates.

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“…Orthotopic implantation is a versatile method allowing to induce tumor relapse at various, pathologically relevant sites in the brain [ 59 ]. The extent and time course of tumor reduction can be closely controlled by induced cell death through the GCV concentration applied.…”

Section: Discussionmentioning

confidence: 99%

Comparing Tumor Cell Invasion and Myeloid Cell Composition in Compatible Primary and Relapsing Glioblastoma

Zhao

Zhang

Uyar

et al. 2021

Cancers

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Glioblastoma (GBM) recurrence after treatment is almost inevitable but addressing this issue with adequate preclinical models has remained challenging. Here, we introduce a GBM mouse model allowing non-invasive and scalable de-bulking of a tumor mass located deeply in the brain, which can be combined with conventional therapeutic approaches. Strong reduction of the GBM volume is achieved after pharmacologically inducing a tumor-specific cell death mechanism. This is followed by GBM re-growth over a predictable timeframe. Pharmacological de-bulking followed by tumor relapse was accomplished with an orthotopic mouse glioma model. Relapsing experimental tumors recapitulated pathological features often observed in recurrent human GBM, like increased invasiveness or altered immune cell composition. Orthotopic implantation of GBM cells originating from biopsies of one patient at initial or follow-up treatment reproduced these findings. Interestingly, relapsing GBM of both models contained a much higher ratio of monocyte-derived macrophages (MDM) versus microglia than primary GBM. This was not altered when combining pharmacological de-bulking with invasive surgery. We interpret that factors released from viable primary GBM cells preferentially attract microglia whereas relapsing tumors preponderantly release chemoattractants for MDM. All in all, this relapse model has the capacity to provide novel insights into clinically highly relevant aspects of GBM treatment.

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

Cited by 42 publications

References 26 publications

PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application

PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application

The Structure, Activation and Signaling of IRE1 and Its Role in Determining Cell Fate

Comparing Tumor Cell Invasion and Myeloid Cell Composition in Compatible Primary and Relapsing Glioblastoma

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