Marion Le GrandFrench Institute of Health and Medical Research | Inserm · Research Center in Oncology of Marseille
Marion Le Grand
PhD, PharmD
About
30
Publications
2,682
Reads
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402
Citations
Citations since 2017
Introduction
I'm a passionate, enthusiastic and highly motivated early-career researcher. I'm interested in the development of novel and effective anticancer strategies. To do that, I combine my knowledge as a trained pharmacist with my understanding of cancer biology.
Additional affiliations
April 2017 - November 2019
Position
- Research Officer
Description
- Focusing on neuroblastoma, my work has made significant contributions towards understanding its pathophysiology and developing new treatments.
April 2016 - March 2017
Position
- Research Associate
Description
- Targeting AKT in neuroblastoma
November 2012 - September 2015
Position
- PhD Student
Description
- Intracellular communication between mitochondria and microtubules: implication in cancer therapeutics.
Education
November 2011 - September 2015
November 2010 - September 2014
Publications
Publications (30)
Synergistic drug combinations are an attractive anticancer strategy but prove challenging to identify. Here we present a stepwise approach consisting in revealing core cancer vulnerabilities and exploiting them through drug combination screen to uncover synergistic treatments for glioblastoma patients.
Methods
We established an innovative method,...
Diffuse midline gliomas (DMGs), including those of the pons (diffuse intrinsic pontine glioma - DIPG), are pediatric CNS tumors recognized as the most lethal of all children’s cancers. Palliative radiotherapy remains the only approved treatment, with survival just 9-11 months post-diagnosis. The brain-penetrant small molecule therapy, ONC201, shows...
Rhabdomyosarcoma (RMS) is the main form of soft-tissue sarcoma in children and adolescents. For 20 years, and despite international clinical trials, its cure rate has not really improved, and remains stuck at 20% in case of relapse. The definition of new effective therapeutic combinations is hampered by the lack of reliable models, which complicate...
Background
Medulloblastoma is the most frequent brain malignancy of childhood. The current multimodal treatment comes at the expense of serious and often long-lasting side effects. Drug repurposing is a strategy to fast-track anti-cancer therapy with low toxicity. Here, we showed the ability of β-blockers to potentiate radiotherapy in medulloblasto...
Diffuse midline gliomas (DMG), including those of the brainstem (diffuse intrinsic pontine glioma - DIPG), are pediatric CNS tumors recognized as the most lethal of all children’s cancers. Palliative radiotherapy is the only approved treatment, with survival just 9-11–months post-diagnosis. ONC201 shows preclinical and emerging clinical efficacy in...
Despite recent advances in deciphering cancer drug resistance mechanisms, relapse is a widely observed phenomenon in advanced cancers, mainly due to intratumor clonal heterogeneity. How tumor clones progress and impact each other remains elusive. In this study, we developed 2D and 3D non-small cell lung cancer co-culture systems and defined a pheno...
Despite recent advances in deciphering cancer drug resistance mechanisms, relapse is a widely observed phenomenon in advanced cancers, mainly due to intratumor clonal heterogeneity. How tumor clones progress and impact each other remains elusive. By better understanding clone dynamics, we could reveal valuable biological insights and unveil vulnera...
The concept of polypharmacology involves the interaction of drug molecules with multiple molecular targets. It provides a unique opportunity for the repurposing of already-approved drugs to target key factors involved in human diseases. Herein, we used an in silico target prediction algorithm to investigate the mechanism of action of mebendazole, a...
Targeting glutamine metabolism has emerged as a potential therapeutic strategy for Myc overexpressing cancer cells. Myc proteins contribute to an aggressive neuroblastoma phenotype. Radiotherapy is one of the treatment modalities for high-risk neuroblastoma patients. Herein, we investigated the effect of glutamine deprivation in combination with ir...
MYCN-amplified neuroblastoma is one of the deadliest forms of childhood cancer and remains a significant clinical challenge. Direct pharmacological inhibition of MYCN is not currently achievable. One strategy could be to target the AKT/GSK3β pathway, which directly regulates the stability of the MYCN protein. Numerous potent and isoform-specific sm...
Stathmin mediates cell migration and invasion in vitro, and metastasis in vivo. To investigate stathmin’s role on the metastatic process, we performed integrated mRNA–miRNA expression analysis to identify pathways regulated by stathmin.
MiRNA and gene arrays followed by miRNA-target-gene integration were performed on stathmin-depleted neuroblastoma...
-amplified neuroblastoma is one of the deadliest forms of childhood cancer and remains a significant clinical problem. Direct pharmacological inhibition of protein is challenging and one possible strategy to treat -amplified neuroblastoma patients is antagonizing proteins involved in its regulation. The AKT/GSK3β pathway directly regulates stabiliz...
-amplified neuroblastoma is one of the deadliest forms of childhood cancer and remains a significant clinical problem. Direct pharmacological inhibition of protein is challenging and one possible strategy to treat -amplified neuroblastoma patients is antagonizing proteins involved in its regulation. The AKT/GSK3β pathway directly regulates stabiliz...
With the aim to obtain a site-specific doxorubicin (DOX) delivery in neuroblastoma SH-SY5Y cells, we designed an hybrid nanocarrier combining graphene oxide (GO) and magnetic iron oxide nanoparticles (MNPs), acting as core elements, and a curcumin–human serum albumin conjugate as functional coating. The nanohybrid, synthesized by redox reaction bet...
There is intense interest in quantifying the levels of microRNA because of its importance as a blood-borne biomarker. The challenge has been to develop methods that can monitor microRNA expression both over broad concentration ranges and in ultralow amounts directly in a patient's blood. Here, we show that, through electric-field-induced reconfigur...
Neuroblastoma is the most common paediatric solid tumor. Approximately half of all neuroblastoma patients are diagnosed with high-risk disease. Amplification of the MYCN oncogene is highly predictive of poor prognosis and occurs in 45% of high-risk neuroblastoma cases. Currently there are no direct inhibitors of MYCN, and outcomes remain below 50%...
Hybrid nanocarrier consisting in nanographene oxide coated by a dextran-catechin conjugate was proposed in the efforts to find more efficient Neuroblastoma treatment with Doxorubicin chemotherapy. The dextran-catechin conjugate was prepared by immobilized laccase catalysis and its peculiar reducing ability exploited for the synthesis of the hybrid...
Metabolic reprogramming is a hallmark of cancer development, mediated by genetic and epigenetic alterations that may be pharmacologically targeted. Among oncogenes, the kinase Akt is commonly overexpressed in tumors and favors glycolysis, providing a rationale for using Akt inhibitors. Here, we addressed the question of whether and how inhibiting A...
Multiple sclerosis (MS) is a neurodegenerative disease characterized by episodes of immune attacks and oligodendrocyte death leading to demyelination and progressive functional deficits. New therapeutic strategies are needed to stimulate the spontaneous regenerative process observed in some patients. Spontaneous myelin repair relies on the mobiliza...
To date, the emergence of drug resistance is never dealt with until it occurs. Yet, studies have shown that treatment-sensitive and -resistant malignant cell subpopulations coexist within the same tumor. Being able to decipher their complex relationship and characterize the impact of intratumor heterogeneity on treatment efficacy is essential to un...
Microtubule-targeting agents (MTAs) are largely administered in adults and children cancers. Better deciphering their mechanism of action is of prime importance to develop more convenient therapy strategies. Here, we addressed the question of how reactive oxygen species (ROS) generation by mitochondria can be necessary for MTA efficacy. We showed f...
Background Deregulation of apoptosis is one of the causes of cancer developing. The Bcl-2 family are central regulators of apoptosis. They are subdivided into two classes, the proapoptotic members (which include Bim) and antiapoptotic members (like Bcl-2). The overexpression of Bcl-2 is generally associated with many cancers and resistance to chemo...
Projects
Projects (4)
A fundamental understanding of the biology of molecular targets in cancer is key for discovering and developing new therapeutic strategies. Based on drug repurposing combined with an innovative concept of reverse molecular pharmacology, our project aims at uncovering novel therapeutic targets and developing more effective treatments for refractory tumors.
To develop innovative nanohybrids to increase drug efficacy in neuroblastoma
To better understand MYCN regulation in order to develop new treatments
