The SIRIC ILIAD Nantes-Angers and the Cancéropôle Grand Ouest are united by a partnership agreement and have launched their first joint call for proposals in November 2019.
This call for proposals aims to support the emergence of innovative or “scientific risk” projects in order to allow the consolidation of preliminary results and to maximise the chances of success in national and international calls for proposals.
Reminder of the eligibility criteria :
- Collaborative project involving at least 1 CGO team (excluding SIRIC) and 1 SIRIC team
- Budget: 40 k€ maximum (joint financing of each by the CGO and the SIRIC)
- To be in line with the themes:
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- Nuclear oncology,
- Study of tumour resistance and its parameters,
- Return to work/epidemiology/public health.
Following evaluations by external experts, the CGO and SIRIC ILIAD are pleased to support two outstanding emerging projects:
“Senescence as an adaptation mechanism to chemotherapy: a new role for tRNA and IRE1”
CHEVET Eric (CGO) Inserm U1242 Rennes Région Bretagne
COQUERET Olivier (SIRIC) CRCINA – Inserm U1232- Team 12 Angers Pays de la Loire Region
Project summary:
Senescence is a tumour suppressor mechanism induced in response to oncogenes or chemotherapy. It theoretically leads to a definitive stop of cell division but doubts have arisen about the impact of this tumour suppression. Recent data published by several laboratories, including the CRCINA, show that some cells escape senescence and acquire new properties that make them more aggressive. Senescence is then incomplete and plays a pro-oncogenic and adaptive role that was not previously suspected.
This project aims to better understand the heterogeneity of senescence and the deleterious effects that this can have. It is based on recent work that describes the pro-oncogenic functions of certain transfer RNAs. Beyond protein translation, some tRNAs promote tumour transformation and metastatic development. An imbalance in tRNA biology leads to amino acid loading errors associated with alterations in the proteome. The latter pose a major question, since it is usually genetic or epigenetic modifications that provide a selective advantage. Bringing together Eric Chevet’s laboratory in Rennes and Olivier Coqueret’s laboratory in Angers, this project will seek to better characterise these new translational functions by studying the role of IRE1 and RtcB proteins in the regulation of tRNAs, escape from senescence and resistance to chemotherapy.
“Innovative hepatotropic petide derivatives labelled with 211At for site-specific targeting of hepatocellular carcinoma (Hepat PepAt)”
LEPAREUR Nicolas. (CGO) Numecan Institute – Nutrition, Metabolism and Cancer Rennes Région Bretagne
CHEREL Michel (SIRIC) CRCINA – Inserm U1232- Team 13 Nantes Pays de la Loire Region
Project summary:
GBVA10-9 and CPB are small synthetic peptides of 18 and 20 amino acids respectively. Screening trials of hepatotropic peptides in the Numecan laboratory have shown that these peptides are strongly taken up by hepatocellular carcinoma cells, and could therefore potentially be used to deliver a radioelement or a cytotoxic agent, and thus target circulating cells and micrometastases responsible for recurrence, which are the main factors limiting the survival of patients. A project currently underway aims to attach an imaging agent (β+ and γ emitter) to these peptides, via different labelling strategies. With the objective of developing a theranostic agent, we are now interested in developing a radiolabelled peptide for therapeutic purposes, and more specifically by an α emitter, more appropriate for targeting small tumour masses. The present project will therefore consist of grafting an α-emitting radionuclide, Astate-211, onto the GBVA10-9 and CPB peptides via different prosthetic groups. The different peptide derivatives obtained will be characterised and their uptake and cytotoxicity will be studied in different cell lines.
In addition, the implementation of this multidisciplinary project will strengthen the links between the partner teams, which could be the starting point for new projects, with new funding and new publications and communications. This project is also part of a larger project, led by the Labex IRON, on the study of the tumour and microenvironmental response after internal radiotherapy vectored by α-emitters, in three tumour models (HCC as a peripheral solid tumour, Multiple myeloma as a disseminated haemopathy and glioblastoma as a confined solid tumour, studied elsewhere in the programme) and with different types of vectors (small molecule, peptide and antibody). This study will establish a rationale between the target, the α-radionuclide vector and their administration modalities influencing the response to radiation.