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Short summaryPersonalized biomarkers can facilitate decision making upon multiple therapeutic options in ccRCC. VEGFR2 expression denoised with 37 normal and tumor gene-expressions relates to sunitinib effect whereas raw VEGFR2 expression doesn’t relate to sunitinib effect.BackgroundSeveral studies suggested that molecular analysis of patients with advanced clear cell renal cell carcinoma (ccRCC) could indicate whether a patient is susceptible of benefiting from sunitinib in first-line systemic treatment compared to immunotherapies. However, data remain conflicting and no predictive biomarker is validated so far to decipher if sunitinib could still represent a good therapeutic option in first line setting and beyond.MethodsPREDMED® denoised the tumor RNA expression of 37 genes including KDR (encoding VEGFR2) estimated by RT-qPCR, by normalizing it on the expression of normal kidney tissue and cell types. We investigated the performance of PREDMED® VEGFR2-scoring to predict the clinical effect of sunitinib for patients affected by ccRCC.ResultsAmong the 34 ccRCC patients’ samples retrospectively retrieved from the UroCCR project (NCT03293563), high VEGFR2 scores were associated with objective clinical responses under sunitinib treatment and low scores with stable disease or progression with a sensitivity of 86%, a specificity of 67% and an AUC of 72.5% (95%CI[50.1–94.9]; p=0.04). VEGFR2 scores were significantly and positively related to progression-free survival (HR = 0.465; 95%CI[0.221–0.978]; p=0.0311) and overall survival (HR = 0.400; 95%CI[0.192–0.834]; p=0.0134) under sunitinib treatment. In our cohort, raw VEGFR2 expression (before PREDMED® processing) was not related to the above mentioned outcomes.ConclusionWe describe a gene-expression based algorithm that is accurately related to the effect of sunitinib for patients with ccRCC. We further plan a validation of PREDMED® for combinatorial strategies involving antiangiogenics and immune-checkpoint blockers.

Resume L’objectif de la table ronde etait d’aborder la place de la neuroimagerie clinique et preclinique dans le developpement de nouveaux medicaments dans les pathologies neurodegeneratives pour la premiere fois lors des rencontres de Giens. Les participants venaient de de l’academie, du monde de la recherche clinique et fondamentale, de l’industrie du medicament et de l’imagerie, de l’Agence nationale de securite du medicament et des produits de sante (ex-Afssaps [Agence francaise de securite sanitaire des produits de sante]). Ils ont fait le constat de l’impact important de la neuroimagerie dans la connaissance des maladies neurodegeneratives, en particulier la maladie d’Alzheimer et dans le developpement des medicaments. Ils ont identifie les differentes approches techniques utilisees, les innovations a venir, des exemples a succes de travail en consortium mais egalement un risque trop important de ne pas pouvoir exploiter la neuroimagerie a tous les niveaux de la recherche. Dans ce contexte, la table ronde a conclu et a propose differentes mesures pour renforcer la place meritee de l’imagerie.

27 pages, 10 figures, 26 references; International audience; Nanomedicine is a relatively new field of science and technology. It looks sometimes ill defined and interpretations of that term may vary, especially between Europe and the United States. By interacting with biological molecules, therefore at nanoscale, nanotechnology opens up a vast field of research and application. Interactions between artificial molecular assemblies or nanodevices and biomolecules can be understood both in the extracellular medium and inside the human cells. Operating at nanoscale allow to exploit physical properties different from those observed at microscale such as the volume/surface ratio. The investigated diagnostic applications can be considered for in vitro as well as for in vivo diagnosis. In vitro, the synthesized particles and manipulation or detection devices allow for the recognition, capture, and concentration of biomolecules. In vivo, the synthetic molecular assemblies are mainly designed as a contrast agent for imaging. A second area exhibiting a strong development is the "nanodrugs" where nanoparticles are designed for targeted drug delivery. The use of such carriers improves the drug biodistribution, targeting active molecules to diseased tissues while protecting healthy tissue. A third area of application is regenerative medicine where nanotechnology allows developing biocompatible materials which support growth of cells used in cell therapy. The application of nanotechnology to medicine raises new issues because of new uses they allow, for instance: Is the power of these new diagnostics manageable by the medical profession? What means treating a patient without any clinical signs? Nanomedicine can contribute to the development of a personalized medicine both for diagnosis and therapy. There exists in many countries existing regulatory frameworks addressing the basic rules of safety and effectiveness of nanotechnology based medicine, whether molecular assemblies or medical devices. But there is a need to clarify or to modify these regulations which mobilize many experts. France is a country where the medical development of nanotechnology is significant, like Germany, the United Kingdom or Spain, as regards the European Union. There is an active scientific community and industrial partners of all sizes, even if the technology transfer to industry is not as effective as in North America.