Creation of new teams: a flagship SIRIC program
A structural impact
Translational research provides the link between basic research, the foundation of knowledge, and clinical research applied to the needs of patients. It aims to transfer discoveries from the bench to the bedside of patients in the form of diagnostic or therapeutic applications. Since its creation, SIRIC has been very involved in the development of new translational research teams.
The new SIRIC teams, led by clinician-researchers or researchers demonstrating a strong link with the clinic ensure a two-way flow of knowledge: from the patient to basic research and from basic research to the patient. Anchored in both cultures and, for the most part, positioned at the heart of the hospital complex in direct connection with actors of the research center these teams constitute a real hub at Institut Curie: a communication crossroads where information and expertise is transferred between research and care.
1st SIRIC label: 5 teams created
Multiple international calls for projects were launched during the SIRIC2011 program. Following a competitive selection by an international jury, 5 new teams were recruited between 2012 and 2017.
- Translational Research in Pediatric Oncology (RTOP)
Gudrun Schleiermacher (Franck Bourdeaut, Co-PI), 2012
The RTOP team is specialized in the study of neuroblastoma and malign rhabdoid tumors. They aim to improve the management of pediatric cancers by characterizing these diseases, studying underlying molecular mechanisms and developing new therapeutic approaches.
- Response to Treatment and Residual Tumor (RT2)
Fabien Reyal, 2012
The RT2 team studies the differences between primary tumor genetic characteristics and those of their residue after treatment. This work, based on human tumors, primary tumor xenografts and breast cancer cell lines is designed to identify predictors of sensitivity or treatment resistance and find ways to circumvent them.
- Translational Research in Immunotherapy
Eliane Piaggio, 2014
TransIm concentrates on 3 research axes : i) the study of the mode of action of immunotherapies ii) the development of new combination immunotherapies iii) the study of immune cells associated with primary tumors and metastatic ganglions
- Dynamics of epigenetic plasticity in cancer (DEpIC)
Céline Vallot, 2017
The team is focused on capturing the dynamic of epigenetic deregulation during tumor progression in vitro and in vivo using an innovative cell model to capture epigenetic alterations in real time. The work mainly concerns breast cancer.
- Integrative functional genomics of cance (IFGC)
Joshua Waterfall, 2017
The objective of the team is to understand how genomic variations within germinal and somatic lines and their regulation stimulate cancer development and therapeutic response. They are developing genomic and computational approaches associated with detailed phenotypic data to understand molecular modifications inducing rare cancers and specific phenotypes.
Scientific results in research and in clinical practice
At the end of the 1st SIRIC label, the work of the teams had already had an impact on clinical practice and research at an international level :
- The RTOP team for example made important contributions to the understanding of the clonal evolution process in neuroblastoma (Bellini et al., Clin Cancer Res. 2015; Schleiermacher et al, J Clin Oncol. 2014) and developed an original method for the clonal evaluation of functional mutations using circulating tumor DNA (Chicard et al., Clin Cancer Res. 2016).
These results have led to a change in clinical practices, particularly through the expert networks that Dr Gudrun Schleiermacher participates in (member of the International Society of Pediatric Oncology Europe (SIOPE), representative of the International Society for Pediatric Oncology Europe Neuroblastoma (SIOPEN), co-president of the International Neuroblastoma Risk Group (INRG), president of the ANRA association (Advances in Neuroblastoma Research Association) and member of the managing committee of the ITCC (Innovative Therapies for Children with Cancer in Europe).
Based on these results innovative clinical trials have been put into place for example MICCHADO (PI Gudrun Schleiermacher) aims to better understand and characterize treatment resistance in children of certain cancers and MAPPYACTS (PI Birgit Georger, IGR, Co-PI Gudrun Schleiermacher) which targets therapeutic stratification in children using high throughput genomics.
Sur la base de ces résultats des essais cliniques innovants ont été mis en place par exemple MICCHADO vise à mieux comprendre et caractériser la résistance aux traitements de certains cancers chez les enfants et MAPPYACTS vise la stratification thérapeutique chez les enfants au moyen de la génomique à haut débit.
- The RT2 team identified several signatures relying on stromal immune infiltration (Bonsang-Kitzis et al, Oncoimmunology, 2015 ; Hamy-Petit et al, Annals of Oncology, 2017) and highlighted the major impact of trastuzumab on HER2-postive tumors (Hamy-Petit et al, British Journal of Cancer, 2016).
- The TransIm team described a novel antibody-drug conjugate targeting the Tn carbohydrate antigen (Sedlik et al, Oncoimmunology, 2016) and then focused on IL2 immunotherapy combination with inhibiting immune pathways (Caudana et al, Cancer Immunology Research, 2019). They developed collaborations with other teams at Institut Curie on gene expression (Le Goux et al, Oncoloimmunology, 2017 ; Lecerf et al, European Journal of Cancer, in press), PI3K pathway inhibition (Borcoman et al, Oncoimmunology, 2019) and in particular a collaboration with 2 other translational research teams (IFGC and RTOP) on the immunogenecity of rhabdoid tumors (in press).
- In collaboration with the ESPCI and HiFiBio the DEpIC team described a new technique profiling thousands of cells at a single cell resolution. Thanks to this technique, they identified a chromatin signature specific to resistant cells (Grosselin et al, Nature Genetics, 2019).
- Joshua Waterfall (IFGC) has been partnered with the Hospital-University Research project ATTRACTion coordinated by Frédéric Rieux-Laucat (Imagine Institute) since 2019 and is also manager of the “Sarcoma” Medico-Scientific Project at Institut Curie.
2nd SIRIC label: perspectives
In the frame of SIRIC a 2nd international call was initiated in September 2018. A translational research team in radio-oncology was identified and arrived at Institut Curie in September 2019.