Marie Dutreix

Marie Dutreix
Institut Curie · Département de Mécanismes moléculaires et oncogenèse

Dr

About

192
Publications
17,311
Reads
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3,733
Citations
Introduction
I work on the characterization of DNA repair mechanisms and damage signaling. I have designed new tools (called DNA baits) to discriminate pathways. Some of them are potent inhibitors of DNA repair and are already tested (with success) in clinical trial to treat local metastasis of Melanoma.
Additional affiliations
August 1998 - November 2000
Yale-New Haven Hospital
Position
  • PostDoc Position
January 1991 - present
Institut Curie
Position
  • Director of research, Head of a team
Description
  • see http://umr3347.curie.fr/fr/equipes-de-recherche/marie-dutreix
June 1988 - December 1990
Yale University
Position
  • PostDoc Position
Description
  • Biochemestry of homologous recombination

Publications

Publications (192)
Article
Full-text available
AsiDNA is a DNA repair inhibitor mimicking DNA double-strand breaks (DSB) that was designed to disorganize DSB repair pathways to sensitize tumors to DNA damaging therapies such as radiotherapy and chemotherapy. We used the property of AsiDNA of triggering artificial DNA damage signaling to examine the activation of DSB repair pathways and to study...
Article
Purpose: Conventional cytotoxic therapies are still the standard of care for the treatment of many cancers. However, the associated severe side effects, especially damage to normal proliferating cells like stem and progenitor cells, often lead to drug dose reduction, which limits treatment success. Indeed, chemotherapy-induced myelosuppression is m...
Article
Full-text available
Aberrant DNA repair pathways that underlie developmental diseases and cancers are potential targets for therapeutic intervention. Targeting DNA repair signal effectors, modulators and checkpoint proteins, and utilizing the synthetic lethality phenomena has led to seminal discoveries. Efforts to efficiently translate the basic findings to the clinic...
Article
Full-text available
Purpose: Medulloblastoma (MB) is an important cause of mortality and morbidity in pediatric oncology. Here we investigated whether the DNA repair inhibitor AsiDNA could help address a significant unmet clinical need in MB care, by improving radiotherapy efficacy without increasing radiation-associated toxicity. Experimental design: To evaluate t...
Article
Full-text available
It is increasingly suggested that ecological and evolutionary sciences could inspire novel therapies against cancer but medical evidence of this remains scarce at the moment. The Achilles heel of conventional and targeted anticancer treatments is intrinsic or acquired resistance following Darwinian selection, i.e. treatment toxicity places the surv...
Article
Full-text available
The clinical management of head and neck squamous cell carcinoma (HNSCC) commonly involves chemoradiotherapy, but recurrences often occur that are associated with radioresistance. Using human SQD9 laryngeal squamous cell carcinoma cancer cells as a model, we aimed to identify metabolic changes associated with acquired radioresistance. In a top-down...
Article
Purpose: One of the main limitations to anticancer radiotherapy lies in irreversible damage to healthy tissues located within the radiation field. "FLASH" irradiation at very high dose-rate is a new treatment modality that has been reported to specifically spare normal tissue from late radiation-induced toxicity in animal models and therefore coul...
Article
Full-text available
Purpose: Carboplatin is used to treat many cancers, but occurrence of drug resistance and its high toxicity remain a clinical hurdle limiting its efficacy. We compared the efficacy and toxicity of DNA repair inhibitors olaparib or AsiDNA administered alone or in combination with carboplatin. Olaparib acts by inhibiting PARP-dependent repair pathway...
Article
Full-text available
Radiation therapy (RT) is widely used in cancer care strategies. Its effectiveness relies mainly on its ability to cause lethal damage to the DNA of cancer cells. However, some cancers have shown to be particularly radioresistant partly because of efficient and redundant DNA repair capacities. Therefore, RT efficacy might be enhanced by using drugs...
Article
Radiotherapy is one of the most common form of treatment in oncology care. Indeed, radiotherapy proved to be very effective in treating a wide range of malignancies. Nevertheless, certain tumours are intrinsically radioresistant or may evolve to become radioresistant. Resistance to radiotherapy is often associated with dysregulated DNA damage respo...
Article
Full-text available
The Achilles heel of anticancer treatments is intrinsic or acquired resistance. Among many targeted therapies, the DNA repair inhibitors show limited efficacy due to rapid emergence of resistance. We examined evolution of cancer cells and tumors treated with AsiDNA, a new DNA repair inhibitor targeting all DNA break repair pathways. Effects of AsiD...
Article
Most anticancer radiation therapy facilities are based on linear electron accelerators with electron–photon conversion providing dose-rates in the range 0.03-0.40 Gy.s⁻¹, and treatment plans usually involve daily fractions of 2 Gy cumulated for up to reaching a total dose close to the limit of tolerance of the normal tissues that surround tumors. W...
Article
Résumé L’ambition du réseau RADIOTRANSNET, labellisé par l’Institut national du cancer (INCa) fin 2018, est de créer un consortium de recherche national dédié à la radiothérapie oncologique préclinique afin de favoriser les interactions scientifiques et cliniques à l’interface de la radiothérapie et de la radiobiologie et de dégager des priorités d...
Conference Paper
The Achilles heel of conventional and targeted anticancer treatments is intrinsic or acquired resistance following Darwinian selection, i.e. treatment toxicity place the surviving cells under intense evolutionary selective pressure to develop resistance. Here, we demonstrate that AsiDNA, the first antitumor drug with an agonist activity, can instea...
Conference Paper
Purpose: Medulloblastoma is paediatric tumor of the cerebellum. It represents the most frequent malignant brain tumor in childhood. It can be classified into four disparate molecular subgroups but current therapies are not yet tailored to their specificities. This is particularly important for subgroups with worse prognosis as Group3. Patients who...
Conference Paper
Purpose: Our laboratory succeeded at developing an original DNA repair inhibitor, called AsiDNATM, developed and tested in clinic by Onxeo. AsiDNATM is a small modified double-stranded DNA molecule vectorised by a covalently bound cholesterol. It acts by inhibiting DNA repair and sensitizes tumors to genotoxic treatments. Here we investigate the di...
Conference Paper
Purpose: Our laboratory succeeded at developing an original DNA repair inhibitor, called AsiDNATM, developed and tested in clinic by Onxeo. AsiDNATM is a small modified double-stranded DNA molecule vectorised by a covalently bound cholesterol. It acts by inhibiting DNA repair and sensitizes tumors to genotoxic treatments. Here we investigate the di...
Conference Paper
The Achilles heel of conventional and targeted anticancer treatments is intrinsic or acquired resistance following Darwinian selection, i.e. treatment toxicity place the surviving cells under intense evolutionary selective pressure to develop resistance. Here, we demonstrate that AsiDNA, the first antitumor drug with an agonist activity, can instea...
Conference Paper
Purpose: Medulloblastoma is paediatric tumor of the cerebellum. It represents the most frequent malignant brain tumor in childhood. It can be classified into four disparate molecular subgroups but current therapies are not yet tailored to their specificities. This is particularly important for subgroups with worse prognosis as Group3. Patients who...
Conference Paper
urpose: Accurate evaluation and prediction of response to anti-cancer treatment remain a great challenge. Stratification biomarkers are of great value to identify responders or non-responders to a specific drug, or even to distinguish between early and delayed responses. In this study, we identified a gene signature to predict AsiDNA treatment effi...
Article
Full-text available
High grade glioma relapses occur often within the irradiated volume mostly due to a high resistance to radiation therapy (RT). Dbait (which stands for DNA strand break bait) molecules mimic DSBs and trap DNA repair proteins, thereby inhibiting repair of DNA damage induced by RT. Here we evaluate the potential of Dbait to sensitize high grade glioma...
Poster
Full-text available
The fight against the cancer requires the development of new strategies in particular in radiotherapy. Because radiotherapy is not always efficient at the hands of tumors known for their resistance at the radiations, we propose the use of nanoparticles as sensitizing agents to improve the killing effect of radiotherapy provided that they enter into...
Presentation
Full-text available
Depuis que la radiothérapie est couramment utilisée dans le traitement du cancer, il est essentiel de développer de nouvelles stratégies qui conduisent à diminuer la dose d'irradiation pour préserver les tissus sains tout en augmentant l'efficacité thérapeutique notamment pour les tumeurs radio-résistantes. Notre nouvelle stratégie est basée sur le...
Article
Purpose: The Achilles' heel of all conventional and targeted anticancer treatments is intrinsic or acquired resistance. The era of precision medicine where tumors are selected for specific treatments based on their genetic alterations is revolutionary, but unfortunately prolonged responses are rarely observed due to rapid emergence of resistant clo...
Article
Purpose: while being registered and used in restricted subset of T-cell lymphoma, HDAC inhibitors (HDACi) have shown limited antitumor effect as single agents. Recent studies have shown an effect of HDACi on DNA damage accumulation, rationalizing their combination with DNA repair inhibitors. In the current study, we propose a novel therapeutic stra...
Chapter
Biological systems need to be robust, both for survival of individuals under stress and for plasticity required for adaptation and evolution. In principle, networks can achieve robustness through redundancy. The most direct mechanism is simple substitutional redundancy, if a protein or a pathway are inactive another protein or pathway can substitut...
Article
Full-text available
Hematologic malignancies are rare cancers that develop refractory disease upon patient relapse, resulting in decreased life expectancy and quality of life. DNA repair inhibitors are promising strategy to treat cancer but are limited by their hematologic toxicity in combination with conventional chemotherapies. Dbait are large molecules targeting th...
Article
Full-text available
Background Radiotherapy plays a major role in the management of high grade glioma. However, the radioresistance of glioma cells limits its efficiency and drives recurrence inside the irradiated tumor volume leading to poor outcome for patients. Stereotactic hypofractionated radiotherapy is one option for recurrent high grade gliomas. Optimization o...
Article
Purpose: PARP inhibitors (PARPi) have shown significant benefits in cancer patients with BRCA mutations. However, their major limitations are the necessity of homologous recombination (HR) deficiency and the rapid emergence of resistance. In the current study, we propose a novel therapeutic strategy, based on drug combination to promote sensitivity...
Article
Therapeutic strategies targeting DNA repair pathway defects have been widely explored, but often only benefit small numbers of patients. Here we characterized potential predictive biomarkers for treatment with AsiDNA, a novel first-in-class DNA repair inhibitor. We evaluated genetic instability and DNA repair defects by direct and indirect assays i...
Article
Objective This study aimed to explore the antitumour effect of the DNA repair inhibitor, DT01 (the cholesterol conjugated form of Dbait), as an adjunct treatment to enhance the therapeutic efficacy of transarterial chemoembolization (TACE) in pre-clinical models of hepatocellular carcinoma (HCC). MethodsA rabbit model bearing liver tumours was eith...
Article
Full-text available
In this review, we present the synthesis of the newly acquired knowledge concerning high dose-rate irradiations and the hopes that these new radiotherapy modalities give rise to. The results were presented at a recent symposium on the subject. Copyright © 2017. Published by Elsevier Masson SAS.
Article
Purpose: Cancer treatments using tumor defects in DNA repair pathways have shown promising results but are restricted to small subpopulations of patients. The most advanced drugs in this field are PARP inhibitors (PARPi), which trigger synthetic lethality in tumors with homologous recombination (HR) deficiency. Using AsiDNA, an inhibitor of HR and...
Article
Full-text available
Common preclinical models for testing anticancer treatment include cultured human tumor cell lines in monolayer, and xenografts derived from these cell lines in immunodeficient mice. Our goal was to determine how similar the xenografts are compared with their original cell line and to determine whether it is possible to predict the stability of a x...
Article
Full-text available
Cold atmospheric pressure plasmas (CAPPs) have emerged over the last decade as a new promising therapy to fight cancer. CAPPs’ antitumor activity is primarily due to the delivery of reactive oxygen and nitrogen species (RONS), but the precise determination of the constituents linked to this anticancer process remains to be done. In the present stud...
Article
Full-text available
Many studies have been devoted to adapting the design of gold nanoparticles to efficiently exploit their promising capability to enhance the effects of radiotherapy. In particular, the addition of magnetic resonance imaging modality constitutes an attractive strategy for enhancing the selectivity of radiotherapy since it allows the determination of...
Article
Full-text available
Background: DT01 is a DNA-repair inhibitor preventing recruitment of DNA-repair enzymes at damage sites. Safety, pharmacokinetics and preliminary efficacy through intratumoural and peritumoural injections of DT01 were evaluated in combination with radiotherapy in a first-in-human phase I trial in patients with unresectable skin metastases from mel...
Article
Full-text available
Anti-cancer drugs often increase reactive oxygen species (ROS) and causeDNAdamage. Here, we highlight a new cross talk between chronic oxidative stress and the histone variant H2AX, a key player inDNArepair. We observe that persistent accumulation ofROS, due to a deficient JunD-/Nrf2-antioxidant response, reduces H2AXprotein levels. This effect is...
Article
Full-text available
Radiolabelled melanin ligands offer an interesting strategy for the treatment of disseminated pigmented melanoma. One of these molecules, ICF01012 labelled with iodine 131, induced a significant slowing of melanoma growth. Here, we have explored the combination of [131I]ICF01012 with coDbait, a DNA repair inhibitor, to overcome melanoma radioresist...
Article
Full-text available
Background Intraperitoneal chemotherapy is limited by tissue penetration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been shown to improve drug uptake by utilizing the physical properties of gas and pressure. This study investigated the effect of adding electrostatic precipitation to further enhance the pharmacologic properties of...