The REMAP-4Kids team, led by biologist Dr Eddy Pasquier and oncopediatrician Prof Nicolas André, draws on the complementary expertise of its members (research biologists, pharmacists and physicians) to establish a continuum from basic research to clinical studies.

Our projects focus on pediatric cancers. The latter have their own pathophysiological characteristics, requiring dedicated research programs. In this context, we have developed an innovative concept of reverse molecular pharmacology, combining high-throughput pharmacological screening with pharmaco-proteomic approaches. Using existing drugs as molecular tools, our approach enables us to identify new combinatorial therapies and study their mechanisms of action. Firstly, we carry out high-throughput pharmacological screening in combination using customized drug libraries. This enables us to identify synergistic combinatorial treatments which are then validated in clinically relevant pediatric cancer models (i.e. 3D spheroids, patient tumoroids, ex vivo organotypic and in vivo orthotopic models). In addition, the interactome of each drug used alone or in combination is characterized by a pharmaco-proteomics method called "thermal proteome profiling".

This unsupervised approach reveals the extent of drug poly-pharmacology (i.e. the action of a drug on several cellular targets in a specific pathological context) and identifies new vulnerabilities in pediatric cancers. Thanks to functional genomics techniques, the pathophysiological roles of new vulnerabilities, particularly in treatment resistance, are studied using a wide range of cell biology techniques.

In this way, we hope to advance our understanding of the molecular mechanisms of refractory pediatric tumors and develop more effective treatments.