Maite Verreault

• PhD
• Researcher at Institut du cerveau et de la moelle

The PI3K/AKT/mTOR pathway is commonly over activated in glioblastoma (GBM), and Rictor was shown to be an important regulator downstream of this pathway. EGFR overexpression is also frequently found in GBM tumors, and both EGFR and Rictor are associated with increased proliferation, invasion, metastasis and poor prognosis. This research evaluated i...

Given compelling evidences supporting the therapeutic potential of irinotecan (IRN) for patients with glioblastoma (GBM), the present study evaluated the activity of Irinophore C™ (IrC™), a lipid-based nanopharmaceutical formulation of IRN, in GBM. The levels of IRN and SN-38 were determined in plasma and brain after a single intravenous dose of IR...

Chemotherapy for glioblastoma (GBM) patients is compromised in part by poor perfusion in the tumor. The present study evaluates how treatment with liposomal formulation of irinotecan (Irinophore C™), and other liposomal anticancer drugs, influence the tumor vasculature of GBM models grown either orthotopically or subcutaneously. Liposomal vincristi...

Background and Purpose Glioblastoma (GBM), the most frequent and aggressive brain tumour in adults, is associated with a dismal prognostic despite intensive treatment involving surgery, radiotherapy and temozolomide (TMZ)‐based chemotherapy. The initial or acquired resistance of GBM to TMZ appeals for precision medicine approaches to the design of...

Antisense oligonucleotides (ASOs) are promising drugs capable of modulating the protein expression of virtually any target with high specificity and high affinity through complementary base pairing. However, this requires a deep understanding of the target sequence and significant effort in designing the correct complementary drug. In addition, ASO...

BACKGROUND Resident microglia are highly plastic myeloid cells. Their phenotype and immune response are determined by the microenvironment composition. Although microglial cells are highly abundant in IDH-mutated (IDHm) gliomas, how this particular environment modulates the transcriptional programs and cell states of these cells remain largely unch...

BACKGROUND Glioblastoma (GBM) is more frequent (sex ratio M:F=1.6) and exhibits worse prognosis in males compared to females suggesting a role of the hormonal macroenvironment including androgen signaling in biology of GBM. In the current study, we studied the impacts of androgen signaling in GBM cells and their immune tissue microenvironment (iTME...

Glioblastoma is currently associated to a dismal prognosis despite intensive treatment involving maximal-safe surgery, radiotherapy and temozolomide (TMZ)-based chemotherapy. Disease progression or relapse is often due to initial or acquired resistance to temozolomide, which may be mediated by the over-expression of the repair enzyme MGMT. To desig...

Diffuse midline gliomas (DMG) are pediatric tumors with negligible two-year survival after diagnosis characterized by their ability to infiltrate the central nervous system. In the hope of controlling the local growth and slowing the disease all patients receive radiotherapy. However, distant progression occurs frequently in DMG patients. Current c...

New therapeutic approaches are needed to improve the prognosis of Glioblastoma (GBM) patients. With the objective of identifying alternative oncogenic mechanisms to abnormally activated EGFR signaling, one of the most common oncogenic mechanisms in GBM, we performed a comparative analysis of gene expression profiles in a series of 54 human GBM samp...

Glioblastomas are characterized by a highly invasive phenotype involving heterogeneous and dynamic molecular effectors. This process is one of the first causes of relapse following standard treatment. In vitro 2D cell migration assays do not recapitulate the biological and cellular microenvironment present in the human brain. Here, human induced pl...

Chemotherapy using temozolomide is the standard treatment for patients with glioblastoma. Despite treatment, prognosis is still poor largely due to the emergence of temozolomide resistance. This resistance is closely linked to the widely recognized inter- and intra-tumoral heterogeneity in glioblastoma, although the underlying mechanisms are not ye...

Background Diffuse midline gliomas (DMG) are pediatric tumors with negligible two-year survival after diagnosis characterized by their ability to infiltrate the central nervous system. In the hope of controlling the local growth and slowing the disease all patients receive radiotherapy. However, distant progression occurs frequently in DMG patients...

Background Patient-derived glioma stem-like cells (GSCs) have become the gold-standard in neuro-oncological research; however, it remains to be established whether loss of in situ microenvironment affects the clinically-predictive value of this model. We implemented a GSC monolayer system to investigate in situ - in vitro molecular correspondence a...

Background: Radiation therapy and chemotherapy using Temozolomide are the standard adjuvant treatments for patients with glioblastoma. Despite maximal treatment prognosis is still poor largely due to the emergence of Temozolomide resistance. This resistance is closely linked to the widely recognized inter- and intra-tumoral heterogeneity in gliobla...

Noncoding RNAs (ncRNAs) play pivotal roles in the regulation of gene expression and represent a promising target for the development of new therapeutic approaches. Among these ncRNAs, microRNAs (miRNAs or miRs) are involved in the regulation of gene expression, and their dysregulation has been linked to several diseases such as cancers. Indeed, onc...

Diffuse midline gliomas H3K27-altered are pediatric tumors associated with dismal survival after diagnosis that are characterized by their ability to infiltrate the entire central nervous system. We show that the extent of tumor invasion and metastatic progression represent critical adverse prognostic factors affecting the survival of DMG patients....

Background Glioblastoma (GBM) is an aggressive brain cancer that typically results in death in the first 15 months after diagnosis. There have been limited advances in finding new treatments for GBM. In this study, we investigated molecular differences between patients with extremely short (≤ 9 months, Short term survivors, STS) and long survival (...

Glioblastoma (GBM) is an aggressive brain cancer that typically results in death in the first 15 months after diagnosis. There have been limited advances in finding new treatments for GBM. In this study, we investigated molecular differences between patients with extremely short (≤9 months, Short term survivors, STS) and long survival (≥36 months,...

The 2-(3-pyridyl)oxazolo[5,4-f]quinoxalines CD-07 and FL-291 are ATP-competitive GSK-3 kinase inhibitors. Here, we investigated the impact of FL-291 on neuroblastoma cell viability and showed that treatment at 10 μM (i.e. ~500 times the IC50 against the GSK-3 isoforms) has no significant effect on the viability of NSC-34 motoneuron-like cells. A st...

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood–brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in prec...

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in prec...

Background New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles, have failed to direct treatment strategies. We hypothesized that interrogation of the GBM tumor microenvironment (TME) and identification of novel TME specific subtypes could inform new...

New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles, have failed to direct treatment strategies. We hypothesized that interrogation of the GBM tumor microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision...

Glioblastoma (GBM) is the most deadly type of malignant brain tumor, despite extensive molecular analyses of GBM cells. In recent years, the tumor microenvironment (TME) has been recognized as an important player and therapeutic target in GBM. However, there is a need for a full and integrated understanding of the different cellular and molecular c...

Background The spectrum of sex differences in glioblastoma (GBM) is a rising topic. GBM is more frequent (sex ratio M:F=1.6) and seem to have worse prognosis in males (M) compared to females. Androgen receptor (AR) is expressed in GBM but its role in GBM biology and clinics is not yet fully understood. Material and Methods We have selected from ou...

Objective: New therapeutic approaches are needed to improve the prognosis of glioblastoma (GBM) patients. Methods: With the objective of identifying alternative oncogenic mechanisms to abnormally activated epidermal growth factor receptor (EGFR) signalling, one of the most common oncogenic mechanisms in GBM, we performed a comparative analysis o...

Background Strategies to modulate the tumor microenvironment (TME) have opened new therapeutic avenues with dramatic yet heterogeneous intertumoral efficacy in multiple cancers, including glioblastomas. Therefore, investigating molecular actors of TME may help understand the interactions between tumor cells and TME. Immune checkpoint proteins such...

Glioblastoma (GBM) is the most frequent and deadliest primary brain cancer in adults, justifying the search for new treatments. Some members of the iron-based ferrocifen family have demonstrated a high cytotoxic effect on various cancer cell lines via innovative mechanisms of action. Here, we evaluated the antiproliferative activity by wst-1 assay...

BACKGROUND Activation of cyclin-dependent kinases (CDKs) contributes to the uncontrolled proliferation of tumour cells. Genomic alterations that lead to the constitutive activation of CDKs are a feature of many tumours including glioblastoma (GBM), the most common and aggressive primary brain tumour. Patient resistance to the current standard of ca...

Activation of cyclin-dependent kinases (CDKs) contributes to the uncontrolled proliferation of tumour cells. Genomic alterations that lead to the constitutive activation or overexpression of CDKs can support tumourigenesis including glioblastoma (GBM), the most common and aggressive primary brain tumour in adults. The incurability of GBM highlights...

SLIT2 is a secreted polypeptide that guides migration of cells expressing ROBO1&2 receptors. Herein, we investigated SLIT2/ROBO signaling effects in gliomas. In patients with glioblastoma (GBM), SLIT2 expression increased with malignant progression and correlated with poor survival and immunosuppression. Knockdown of SLIT2 in mouse glioma cells and...

Due to the absence of curative treatments for glioblastoma (GBM), we assessed the efficacy of single and combination treatments with a translationally relevant 2nd generation TRAIL-receptor agonist (IZI1551) and the blood–brain barrier (BBB) permeant proteasome inhibitor marizomib in a panel of patient-derived glioblastoma cell lines. These cells w...

Purpose Strategies to modulate the tumor microenvironment (TME), including the vascular and immune components, have opened new therapeutic avenues with dramatic yet heterogeneous intertumor efficacy in multiple cancers, including brain malignancies. Therefore, investigating molecular actors of TME may help understand the interactions between tumor...

Background Strategies to modulate the tumor microenvironment (TME) have opened new therapeutic avenues with dramatic yet heterogeneous intertumoral efficacy in multiple cancers, including glioblastomas. Therefore, investigating molecular actors of TME may help understand the interactions between tumor cells and TME. Immune checkpoint proteins such...

SLIT2 is a secreted polypeptide that guides migration of cells expressing ROBO1&2 receptors. Herein, we investigated SLIT2/ROBO signaling effects in gliomas. In patients with glioblastoma (GBM), SLIT2 expression increased with malignant progression and correlated with poor survival and immunosuppression. Knockdown of SLIT2 in mouse glioma cells and...

Glioblastoma (GBM) is the most frequent and aggressive primary cancer of the brain in adults. Despite aggressive therapeutic interventions, the median overall survival is below 18 months after initial diagnosis. The current standard of care for patients with newly diagnosed GBM includes concurrent administration of temozolomide (TMZ) and radiothera...

Glioblastoma (GBM) is the most frequent and aggressive adult brain tumor with 85% of patients dying within two years. New effective precision medicine therapies are urgently required, especially for isocitrate dehydrogenase wild-type (IDHwt) disease. Despite efforts to subtype patients based on molecular profiles, this approach has yet failed to di...

Glioblastoma (GBM) represents the most common primary malignancy of the central nervous system in adults, and remains a largely incurable disease. The elucidation of disease subtypes based on mutational profiling, gene expression and DNA methylation has so far failed to translate into improved clinical outcomes. However, new knowledge emerging from...

p>High tumor mutational burden (hypermutation) is observed in some gliomas; however, its mechanisms of development and whether it predicts immunotherapy response are poorly understood. Here, we comprehensively analyze the molecular determinants of mutational burden and signatures in 10,294 gliomas including AACR Project GENIE and institutional data...

Glioblastoma (GBM) is the most aggressive malignant primary brain tumour with a median overall survival of 15 months. To treat GBM, patients currently undergo a surgical resection followed by exposure to radiotherapy and concurrent and adjuvant temozolomide (TMZ) chemotherapy. However, this protocol often leads to treatment failure, with drug resis...

A high tumour mutational burden (hypermutation) is observed in some gliomas1–5; however, the mechanisms by which hypermutation develops and whether it predicts the response to immunotherapy are poorly understood. Here we comprehensively analyse the molecular determinants of mutational burden and signatures in 10,294 gliomas. We delineate two main p...

Glioblastoma (GBM) is a highly infiltrative brain cancer, which is thus difficult to operate. GBM cells frequently harbor Epidermal Growth Factor Receptor amplification (EGFRwt) and/or activating mutation (EGFRvIII), generating at least two different cellular subpopulations within the tumor. We examined the relationship between the diffusive archit...

BACKGROUND Hypermutation is an emerging biomarker for predicting response to immunotherapy in cancer patients, however its clinical value in gliomas is not established. We sought to assess the determinants of hypermutation in gliomas, and its value for predicting response to standard of care and immune checkpoint blockade (ICB). METHODS We perform...

Introduction Glioblastoma (GBM) is the most common and aggressive primary brain cancer in adults. Few cytotoxic chemotherapies have been shown to be effective against GBM, due in part to the presence of the blood–brain barrier (BBB), which reduces the penetration of chemotherapies from the blood to the brain. Ultrasound-induced BBB opening (US-BBB)...

ATP-binding cassette transporters (ABC transporters) regulate traffic of multiple compounds, including chemotherapeutic agents, through biological membranes. They are expressed by multiple cell types and have been implicated in the drug resistance of some cancer cells. Despite significant research in ABC transporters in the context of many diseases...

The names of authors Marc Sanson and Jean-Yves Delattre were incorrectly presented in the initial online publication. The original article has been corrected.

Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA D463H mutation. PRKCA encodes the Protein kinase C (PKC) isozyme alpha (PKCα) and is mutated in...

BACKGROUND Chordoid glioma (ChG) is a characteristic, slow growing and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. METHODS We analyzed primary chordoid glioma samples by whole exome sequencing, RNAseq, Sanger sequencing, RT-PCR and immunohistochemistry. We determined subcellular localization, kinase activity and e...

Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenici...

Background Glioblastoma (GBM) is the deadliest primary brain cancer in adults. Emerging innovative therapies hold promise for personalized cancer treatment. Improving therapeutic options depends on research relying on relevant preclinical models. In this line we have established in the setting of the GlioTex project (GBM and Experimental Therapeuti...

Introduction: Glioblastomas (GBM) are the most common and aggressive primary malignant brain tumors in adults. The blood brain barrier (BBB) is a major limitation reducing efficacy of anti-cancer drugs in the treatment of GBM patients. Areas covered: Virtually all GBM recur after the first-line treatment, at least partly, due to invasive tumor c...

Our laboratory reported that Irinophore C™ (IrC™; a lipid-based nanoparticulate formulation of irinotecan) is effective against an orthotopic model of glioblastoma (GBM) and that treatment with IrC™ was associated with vascular normalization within the tumor. Here, the therapeutic effects of IrC™ when used in combination with temozolomide (TMZ) in...

Purpose: p53 pathway alterations are key molecular events in glioblastoma (GBM). MDM2 inhibitors increase expression and stability of p53 and are presumed to be most efficacious in patients with TP53 wild-type and MDM2-amplified cancers. However, this biomarker hypothesis has not been tested in patients or patient-derived models for GBM. Experime...

Alteration of P53 pathway is one of the key molecular events involved in glioblastoma (GBM) biology. Genetic alterations which reduce TP53 function in GBM include MDM2 amplification (14% of patients), MDM4 amplification (7%), and TP53 gene mutations (35%), each of which is generally thought to be mutually exclusive. The study presented here aims to...

Glioblastoma multiforme (GBM) ranks among the deadliest types of cancer and given these new therapies are urgently needed. To identify molecular targets, we queried a microarray profiling 467 human GBMs and discovered that polo-like kinase 1 (PLK1) was highly expressed in these tumors and that it clustered with the proliferative subtype. Patients w...

A number of studies have outlined the antiangiogenic effects of cytotoxic agents when administered frequently at low doses. These studies suggest that the effect of the cytotoxic agent is on the vasculature within the tumor and it is assumed that there is little or negligible cytotoxicity. Liposomal drug delivery systems have the ability to provide...

Glioblastoma (GBM) cell lines expressing red fluorescent proteins were evaluated as a tool for non-invasive imaging of orthotopic tumors. mKate2- and mCherry-transduced U251MG GBM lines were sorted by flow cytometry. The growth rates and drug sensitivity of the resulting cell lines were compared to those of the parental line. Following orthotopic i...

Short interfering RNA targeting ILK (ILK siRNA) could be used to treat patients with cancers where constitutive activation of the AKT/PI3K pathway is prominent (e.g., those cancers lack functional PTEN). It is generally believed that siRNA therapeutics will require the use of delivery systems and lipid-based formulations containing cationic lipids...

Integrin-linked kinase (ILK) was assesed as a therapeutic target in glioblastoma xenograft models through multiple endpoints including treatment related changes in the tumor microenvironment. Glioblastoma cell lines were tested in vitro for sensitivity toward the small-molecule inhibitors QLT0254 and QLT0267. Cell viability, cell cycle, and apoptos...

Developing novel synergistic and more effective combination treatments is necessary for better management of breast cancer in the clinic. It is established that HER-2 overexpressing breast cancers are sensitive to the HER-1 (epidermal growth factor receptor (EGFR)) inhibitor gefitinib, but that this targeted agent produces only moderate therapeutic...

The advent of sophisticated experimental tools that can probe the molecular pathology of cancer has revealed a number of genes and gene families that could prove attractive targets for cancer therapy. Thus, gene silencing strategies have been envisioned to treat cancer by targeting the cancer cell's capacity to: (I) resist conventional treatment me...

The present study uses cell-based screening assays to assess the anticancer effects of targeting phosphatidylinositol 3-kinase-regulated integrin-linked kinase (ILK) in combination with small-molecule inhibitors of Raf-1 or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK). The objective was to determine if...

A rat model of acute pulmonary air embolism (APAE) was developed. These animals had a higher right ventricular systolic pressure (RVSP) (+ 69% at 15-minute peak, and 21-34% at 30-180 minutes), as well as a reduced mean arterial blood pressure (10-20% at 60-180 minutes), heart rate (20-26% at 60-180 minutes) and PaO2 (9-11% at 30-180 minutes) compar...