The TRAJECTORY project has received funding from the French National Research Agency (ANR) as part of its call for projects “Setting up European or International Scientific Networks – MRSEI 2023 “.
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About TRAJECTORY
Training the next generation of researchers to model and target intratumour heterogeneity (ITH) in cancer relapse
TRAJECTORY is an interdisciplinary and intersectoral research and training consortium project, supported by ANR, the French National Research Agency, consisting of 12 beneficiaries and 22 associated partners brought together under the HORIZON-MSCA-2024-DN-01-01 call (Marie Skłodowska Curie Actions) . If funded, TRAJECTORY will aim to provide a training programme for PhD students from different sectors across Europe and to enhance their long-term employability in the field of tumour heterogeneity.
Christophe GINESTIER, Inserm
Project coordinator – Brainstorming meeting, Marseille, September 2023
Research
Deciphering the biology of tumour relapse and developing optimised therapeutic strategies to better treat patients
Nowadays the leading cause of cancer death in patients with solid tumors is the occurrence of local or distant recurrences after the first lines of treatment. Cancer relapses have a significant enrichment in treatment-resistance cells compared to primary tumors. This is because therapeutic pressure imposes additional stresses that contribute to tumor evolution and the acquisition of resistance .
Different mechanisms of failure can explain our difficulties to treat relapsing patients. First, each solid tumor is composed of cancer cells heterogeneous in terms of their genetic, epigenetic, transcriptional and translational states that evolve under treatment pressure . If advances in genomic technologies, single-cell sequencing and spatial transcriptomics have allowed to depict a thorough ITH portrait of primary tumors, very little has been done to characterize cancer relapse ITH. Leveraging transitions dynamics between cellular states appears as a potential therapeutic strategy to target tumor relapses. Second, preclinical models are often not established in relapsed conditions whereas early phase clinical trials are implemented in relapsing diseases, where patients have already received one or several lines of therapy. This may explain why the attrition rate in oncology drug development is among the worst in the drug development pipeline. The challenges of the future will be to propose adapted OMICs analysis and to develop relevant experimental design to decipher tumor relapses biology and to offer optimized therapeutic strategies to better treat patient with recurrences.
Eduard BATLLE, IRB Barcelona
Beneficiary – Brainstorming meeting, Marseille, September 2023
Training
At TRAJECTORY, we support the idea, that in order to advance in the implementation of adapted therapeutic approaches to treat relapsing patients, the next generation of early-stage researchers (ESRs) should i) be aware of the limitations and shortcomings of the current methodology used to explore ITH, ii) have a multidisciplinary approach to their future research project ii) engage in the validation, standardization, and implementation of clinically relevant models. Therefore, the main scientific objectives of TRAJECTORY are to combine the most advanced technologies to study ITH in cancer relapses while focusing on training.
Eduard BATLLE, IRB Barcelona
Beneficiary – Brainstorming meeting, Marseille, September 2023
Interdisciplinarity
Philosophical concepts to redefine intratumor heterogeneity
Over the last decade, the concept of ITH has been an overwhelming tidal wave in the scientific community studying cancer. It introduces several notions and concepts such as cancer stemness, cell plasticity, clonal evolution or tumor ecosystem. The resulting emulation strongly stimulates research activity but also challenges our current vision of this disease and unveils deep semantic and conceptual problems in the field. In TRAJECTORY, we will not only drive scientific innovation, but also guide the next generation of scientists to conceptualize ITH from both biological and philosophical issue.We propose in workpackage 1, to train doctoral candidates to introduce ontology in their biological theories. We believe that it is crucial to clarify notions sustaining the concept of ITH to be more efficient to develop new therapeutic strategies against cancers.
Lucie LAPLANE, UoP
WP1 leader – Brainstorming meeting, Marseille, September 2023
Original communication strategy
Tr(ART)jectory, a collaborative art-science project with ESAAIX students
The École Supérieure d’Art d’Aix-en-Provence (ESAAIX) Félix Ciccolini is a public establishment for cultural cooperation, dedicated to higher education and research in the arts. ESSAIX prepares students for the Diplôme National d’Art (DNA, equivalent to a bachelor’s degree) and the Diplôme National Supérieur d’Expression Plastique (DNSEP, equivalent to a master’s degree). It also supports a doctoral program in creative research, validated within the framework of the Locus sonus vitae research laboratory, under joint supervision with Aix-Marseille University and other laboratories (IREMAM, CNRS, IMERA). ESSAIX is also active in disseminating, promoting and providing expertise in the field of contemporary art, organizing exhibitions, lecture series and symposia. ESAAIX is a cultural partner of TRAJECTORY.
As part of our future communication initiatives, we’ll be offering future doctoral candidates the opportunity to participate in Tr(ART)jectory, a collaborative art-science project with a group of students and recent graduates from ESAAIX. Tr(ART)jectory aims to raise public awareness of the study of tumor heterogeneity as a means to prevent and treat cancer, and to expose our young researchers to new ways of thinking, enabling them to develop their vision of their research projects and future careers.
During the development stages of Tr(ART)jectory, students will have the opportunity to meet face-to-face and via videoconferencing to develop their projects. The resulting works of art will be presented at a public workshop in Amsterdam (consortium midterm meeting, month 24) and broadcast through our website and social networks.