European programs

European Programs

Biomedical research is strongly linked to the European context. Researchers are encouraged and guided in their participation in the various Horizon 2020 programmes, the main instrument for implementing European research.

CRCT researchers are fully engaged in these calls for proposals. Find below all the European programmes in which the CRCT is strongly involved.

PROTEOblood – New therapies against two subtypes of leukemias and lymphomas.

Significant advances have been made recently in the diagnosis and selective treatment of some blood cancers. However, most of these cancers remain incurable. Much evidence suggests a link between imbalances in protein homeostasis and the development of some subtypes of leukemia and lymphoma. The study of this phenomenon requires highly specialized knowledge and represents a fundamental economic and research challenge, which institutions cannot address efficiently on an individual basis.

Researchers from universities, research centers, and companies in France and Spain have joined together to create a French-Spanish cooperative network for the analysis of proteinopathies and the development of individualized therapies in hematological cancers: EFA360/19 PROTEOBlood. This network will investigate protein homeostasis in two prevalent subtypes of leukemia and lymphoma and develop personalized treatments to cure them.

PROTEOblood’s goal is to optimize, share and exploit a set of cutting-edge technologies and resources through the coordination of these entities, for the study of protein homeostasis in two prevalent subtypes of leukemia and lymphoma, and to generate innovative tools and technologies transferable to the development of personalized medicines against these diseases.

To this end, the network will bring together a collection of study models derived from patients (organoids and xenografts) with the capacity to recreate the tumor microenvironment ex vivo. State-of-the-art proteomics approaches, associated with systems biology analysis and small molecule design, will allow the complete characterization of proteinopathies and the development of effective and safe therapies to validate in organoid and xenograft collections. PROTEOblood will thus promote technological development, cross-border cooperation, and knowledge sharing, easing the optimization of existing infrastructures and resources of all entities.

CRCT program partnership Jean Emmanuel Sarry 

More : https://www.poctefa.eu/fr/listes-de-projets/detail-du-projet/?IdProyecto=919a3a25-ec03-4fed-9528-1e6d883683ff

Date of begining : june 2020
date of closure : may 2022

The project has been co-financed at 65% by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra Programme (POCTEFA 2014-2020). https://www.poctefa.eu/fr/

Press release june, 23, 2020 (june 23, 2020)

MITHAML – Metabolic heterogeneity in acute myeloid leukaemia

Accumulating evidence indicates that metabolism could be implicated in the drug resistance that develops in acute myeloid leukaemia (AML). However, approaches so far have assessed metabolism in bulk, without addressing the genotypic and phenotypic heterogeneity observed in cancer. The EU-funded MITHAML project will employ mass cytometry (CyTOF), a single-cell technology with tremendous analytical potential to investigate the role of metabolic intra-tumour heterogeneity before and after therapy. By focussing on metabolism-targeting drugs, researchers hope to find new therapeutic targets against AML. Deciphering the role of metabolism in chemoresistance will open new avenues for therapy with new combinations of drugs.

This program will be carried out thanks to a collaboration between the laboratory of Dr K Davis (Stanford University, San Francisco, USA), very recognized in the study of intratumor heterogeneity in particular with Cytof, and the laboratory of Dr JE Sarry (CRCT Inserm, Toulouse, France), expert in the role of oncometabolism in the in vivo resistance of LAM. Finally this project will be led by Dr L Stuani who will spend two years in Stanford before coming to establish him in Toulouse.

This program is coordinated by Jean emmanuel Sarry 

More : https://cordis.europa.eu/project/id/897140

Date of begining : 21 septembre 2020
date of closure : 20 septembre 2023

This research programme is part of the European call H2020-MSCA-IF-2019 (Marie Skłodowska-Curie Actions- Individual fellowship)

IMMUSPHINX - Targeting sphingolipid metabolism to improve anti-melanoma immune therapies

Immune checkpoint inhibitors (ICI) have shown unprecedented and long-lasting anti-tumor response in patients with metastatic melanoma. To extend the proportion of responders, prevent cancer recurrence and improve the efficacy in other cancers, novel strategies are urgently needed. Also, personalized therapies, based on robust prognostic and predictive factors, are necessary to resource allocation and toxicity management.

We recently discovered that sphingolipid (SL) metabolism is strongly altered in melanoma, leading to oncometabolites that modify the tumor microenvironment. Unpublished preclinical data reveal that SLs critically regulate tumor progression and anti-melanoma immune responses. We hypothesize that: (i) SL blocking agents (SBA) synergize with ICI in inducing anti-tumor responses and (ii) SL levels and/or SL-metabolizing enzymes constitute useful biomarkers predictive of prognosis and treatment outcome in response to ICI. IMMUSPHINX aims at developing new combined therapeutic strategies that target both SL metabolism and immune checkpoints.

Moreover, to individualize new immune modulating therapies, IMMUSPHINX aims at identifying prognostic and/or predictive biomarkers. Specifically, IMMUSPHINX will determine: (i) the efficacy of novel approaches combining SBA with ICI; (ii) how SLs affect tumor microenvironment and facilitate anti-melanoma immune responses by analyzing the sphingolipidome of tumors and plasma, and by identifying immune signatures; (iii) whether intratumoral SL metabolizing-enzymes and/or peripheral blood SLs could serve as biomarkers predictive of ICI efficacy. These parameters as well as treatment efficacy in melanoma patients will be analyzed using (Ir) RECIST both in a retrospective and prospective manner.

Overall, IMMUSPHINX is an essential step to (i) define the eligibility criteria for this novel strategy combining SBA and ICI, and (ii) set up a clinical trial using SBA as adjuvants for immune-based therapies in cancer patients.

This program is coordinated by Nathalie Andrieu-Abadie

More : https://www.transcanfp7.eu/index.php/abstract/immusphinx.html

Date of begining : April,1, 2017
Date of closure : june, 30, 2021

This research programme is part of the European call ERA-NET TRANSCAN-2 Aligning national/regional translational cancer research programmes and activities

Part of the objectives of this project was published in 2020::

Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1.
Imbert C, Montfort A, Fraisse M, Marcheteau E, Gilhodes J, Martin E, Bertrand F, Marcellin M, Burlet-Schiltz O, Peredo AG, Garcia V, Carpentier S, Tartare-Deckert S, Brousset P, Rochaix P, Puisset F, Filleron T, Meyer N, Lamant L, Levade T, Ségui B, Andrieu-Abadie N, Colacios C.
Nat Commun. 2020 Jan 23;11(1):437

 

PINICAL-MRT : Protocols for clinical impact in molecular radiotherapy

Developing the guidance to translate measurement knowledge on Molecular Radiotherapy into clinical practice

Article 56 of EC Directive 2013/59/EURATOM, detailing the requirements for individual dose planning for radiotherapy patients, is being introduced across EU states. This applies to Molecular Radiotherapy (MRT), which involves the use of radiopharmaceuticals in cancer treatment, but currently no standardised methods exist to support clinical compliance. A traceable MRT calibration infrastructure for patient-tailored doses was developed in the EMRP project MetroMRT and EMPIR project MRTDosimetry however before this can be transferred to the clinic it requires extending and staff trained in its use.

The project will develop guidance on how to use the protocols and methods developed in MRTDosimetry and enable traceable practices to be established within clinical centres. This will include how to calibrate, commission and perform quality control for quantitative imaging instruments used for dosimetry. Training materials will also be developed to support measurement practices. At the end of the project the establishment of standard practices for MRT will make it easier for relevant government agencies to ensure compliance with regulations as well as deliver more accurate, better targeted treatments for patients.

CRCT Partners Manuel Bardiès

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Date of begining : 2020
Date of closure : 2021

This research program is part of the European call EURAMET – The European Association of National Metrology Institutes

MEDIRAD - Implications of Medical Low Dose Radiation Exposure

MEDIRAD’s context

The evolution of medical science and the growing pace of innovation and deployment of medical technology have led to a situation where most of the artificial ionising radiation exposure of the European population is created by diagnostic imaging or radiotherapy procedures.

The use of ionising radiation in medicine has been steadily increasing, and this trend is set to continue, with obvious health benefits for the population thanks to improved diagnostic and therapy technologies. However, the increasing use of new modalities both for diagnosis and treatment also raises a number of issues in radiological protection of patients and medical workers, as the population’s average medical exposure levels are continually rising.

Although most of these exposures result in low to moderate doses in most tissues, there is a need to evaluate the health effects of these exposures, optimise practices to reduce doses and develop dose evaluation tools that can be used in clinical practice to ensure adequate and improved radiation protection of patients and medical personnel. Whilst patient RP has been a constant concern of physicians, and regulated by the competent authorities, some specific scientific questions arise in this context, which RP research has not addressed before, at least successfully.

Objectives

MEDIRAD aims to enhance the scientific bases and clinical practice of radiation protection in the medical field and thereby addresses the need to better understand and evaluate the health effects of low-dose ionising radiation exposure from diagnostic and therapeutic imaging and from off-target effects in radiotherapy.

This will be achieved by focusing on three major operational objectives:

  1. Improvement of organ dose estimation and registration in order to a) inform clinical practice, optimise doses and set recommendations and b) provide adequate dosimetry for clinical-epidemiological studies of effects of medical radiation.
  2. Evaluation of the effects of medical exposures, focusing on the two major endpoints and exposure conditions of public health and clinical relevance:
    • Cardiovascular effects of low to moderate doses of radiation from radiotherapy including understanding of mechanisms
    • Long term effects of low doses from higher dose radiological procedures on the risk of cancer
  3. Development of science-based policy recommendations for decision-makers and practitioners for the effective protection of patients, workers and the general public.

CRCT Partners Manuel Bardiès, Frédéric Courbon

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Date of begining : June 1, 2017
Date of closure : February 28, 2022 

This research program is part of the European call Horizon 2020 – Euratom : https://www.horizon2020.gouv.fr/pid30040/euratom.html

IMLINFO : Cross-border Network of Personalized Immunotherapies for Non-Hodgkin's Lymphomas

IMLINFO is a cross-border network of personalized immunotherapies for Non-Hodgkin’s lymphomas (NHL) involving 7 organizations located in Spain and France. Its main objective is to determine the efficacy of new immunotherapy treatments through the creation of a NHL repository associated to a 3-dimensional (3-D) culture.

IMLINFO is formed by a multidisciplinary team with experts in 3-D culture systems, multicellular cultures, as well as in its structural characterization and drug penetrability by state-of-the-art microscopy. Likewise, the pharmaceutical company integrated in IMLINFO contributes its proven experience in the development of small molecules as innovative immunotherapies already licensed to international pharmaceutical companies. In order to move towards a personalized medicine, cross-border cooperation is paramount for obtaining a large number of samples from NHL patients coming from hospitals in the POCTEFA territory along with scientific -technological collaboration.

 

CRCT Partners Christine Bezombes

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Date of begining : 01/01/2018
Date of closure : 31/12/2021

This research program is part of the European call POCTEFA : https://www.poctefa.eu

  

MRTDosimetry : Metrology for clinical implementation of dosimetry in molecular radiotherapy

The use of radiopharmaceuticals for treating cancer in Europe has grown considerably over the last few years. Current practice is to administer a carefully measured radioactivity dose to a patient, without taking into account the amount of radioactivity actually absorbed by tissue in the patient’s body. As a result, the administered dose is not the best indicator of effective treatment, and accurate knowledge of the radioactivity absorbed by tissue would make a significant difference to the success of many patients’ treatments. A recent EU Directive (2013/59/EURATOM) will require individual dose planning based on absorbed dose measurements for patients from February 2018. However, the planning process is complex and no standard methods exist to support clinics’ compliance with the regulation. This project addressed these obstacles by building on the work of previous EMRP project HLT11 MetroMRT, developing a robust measurement protocol and providing standardised methods, test objects and resources to support molecular radiotherapy clinics in setting up and validating dosimetry, thereby improving patient outcomes.

CRCT Partners Manuel Bardiès

More : http://mrtdosimetry-empir.eu/

Date of begining : 2016
Date of closure : 2019

This research program is part of the European call EURAMET – The European Association of National Metrology Institutes

ONCONET SUDOE : European Network for translational Research and Innovation in oncology
The various types of cancer are universal chronic diseases that are nowadays one of the main causes of death. Several member states of the European Union have drawn up specific public policies regarding cancer, but these policies are not currently subject to transverse comparative studies. This is precisely the objective of the ONCONET SUDOE project: analysing and comparing in each territory of the south-west European network the public health policies as to prevention, diagnosis, therapeutic innovation, and the use of information and communication technologies in the administration of patients. This approach may give rise to the pooling of certain resources and the equalisation of professional practices.

CRCT Partners Pierre Cordelier

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This research program is part of the European call INTERREG Sudoe : https://www.interreg-sudoe.eu/gbr/home

ALKATRAS : Role of miRNA and RNA binding proteins (RNA-BPs) in the regulation of the autophagy signalling pathway in ALK dependent tumours

A wide array of deregulated miRNAs has previously been defined by a number of ERIA members in ALK-induced malignancies and has potential diagnostic utility. Since the miRNA targeted sequences and the RNA-BP binding sites are often close or overlapping, the question of cross-talk between these two RNA modulators will be investigated in terms of classical (proliferation, survival, invasion) and emerging (autophagy, ER Stress) mechanisms of tumorigenesis.

We specifically aim to: Investigate the regulation of autophagy signalling by miRNAs and RNA-BPs or epigenetic modifications; determine the role of autophagy, using classical autophagy assays, in ALCL, NSCLC and neuroblastoma cell lines and mouse models; test whether autophagy inhibition can potentiate the efficacy of ALK inhibition by Crizotinib and other second generation inhibitors.

CRCT Partners : Sylvie Giuriato, Domenico Sorrentino

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This research program is part of the European call Horizon 2020 Marie Skłodowska-Curie Innovative Training Networks (ITN-ETN) : https://www.horizon2020.gouv.fr/cid144802/appel-2020-innovative-training-networks-itn.html

Phd - Deciphering PI3K biology in health and disease
The Phosphoinositide 3-kinase (PI3K) pathway is at the core of multiple fundamental biological processes controlling metabolism, protein synthesis, cell growth, survival, and migration. This inevitably leads to the involvement of the PI3K signalling pathway in a number of different diseases, ranging from inflammation and diabetes to cancer, with PI3K pathway alterations present in almost 80% of human cancers. Therefore, PI3Ks have emerged as important targets for drug discovery and, during 2014, the first PI3K inhibitor was approved by FDA in the US for the treatment of a lymphocytic leukaemia. Nonetheless, our understanding of PI3K-mediated signalling is still poor and only a fraction of the potential therapeutic applications have been addressed so far, leaving a large amount of translational work unexplored. Europe features a set of top quality research institutions and pharmaceutical companies focused on PI3K studies but their activities have been so far scattered. This proposal fills this gap by providing a multidisciplinary network (biochemistry, mouse studies, disease models, drug development, software development) and an unprecedented training opportunity from the bench to the bedside (from pre-clinical discoveries to clinical trials), through cutting edge molecular biology, drug discovery and clinical trial organization. The proposal is aimed at training young investigators in deep understanding of the different PI3K isoforms in distinct tissues and to translate this knowledge into a new generation of PI3K inhibitors, treatment modalities and into identify new uses for existing PI3K inhibitors.

CRCT Partners (co-coordinator) : Julie Guillermet-Guibert

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This research program is part of the European call Horizon 2020 Marie Skłodowska-Curie Innovative Training Networks (ITN-ETN) : https://www.horizon2020.gouv.fr/cid144802/appel-2020-innovative-training-networks-itn.html