Reverse Molecular Pharmacology in pediatric oncology (REMAP-4Kids)

The Pasquier / André team is part of the Translate-it department

Using existing drugs to reveal the vulnerabilities of pediatric cancers and improve patient care.

 
 
REMAP-4Kids is a multi-disciplinary team led by cancer biologist Dr Eddy Pasquier and pediatric oncologist Prof Nicolas André, and composed of scientists, pharmacists and clinicians. Our research program builds on an integrative approach that we have recently developed and termed reverse molecular pharmacology, which combines high-throughput screening and pharmaco-proteomics. Our approach is applied to childhood cancers, which have singular features that are not found in adult cancers, requiring dedicated research programs.

Using existing drugs as molecular tools, our work leads to a better understanding of the biology of pediatric cancers and to the discovery of new therapeutic targets. Indeed, our original and integrative workflow aims at identifying potent drug combinations and deciphering their mechanism(s) of action in tumor cells.

To do that, we perform upfront combination drug screens using custom-made drug libraries to first reveal potentially synergistic drug associations, which are then validated in clinically-relevant models of pediatric cancers (3D tumor spheroids, patient-derived tumoroids, ex vivo organotypic co-cultures and in vivo models). Once validated, the interactome of each drug individually and in combination is characterized by a pharmaco-proteomics method called thermal proteome profiling.

This unsupervised approach can reveal the full extent of the poly-pharmacology of a drug of interest (i.e. the capacity of a given drug to interact with multiple molecular targets in a specific cellular context), thus potentially unveiling novel actionable vulnerabilities in pediatric cancers. The biological role of these targets is then studied using functional genomics combined with a large panel of cell biology assays, to define their role in the clonogenicity, stemness and resistance to treatment of pediatric tumors.

The overall objective of the REMAP-4Kids team is to both improve our knowledge in pediatric cancer biology and identify innovative therapeutic strategies.

Keywords

• Drug poly-pharmacology (i.e. the capacity of a given drug to interact with multiple molecular targets in a specific cellular context)
• Pharmaco-proteomics (i.e. to uncover the cellular interactome of drugs using mass spectrometry)
• Pediatric oncology 
• Translational research

Team publications