Biology for Treatments of Drug-Resistant Cancers in Children

Advanced cancers are the leading cause of death among children, adolescents, and young adults due to primary and secondary resistance to current treatments. The team founded the MappyActs pediatric precision medicine program and is developing new therapeutic strategies for advanced cancers through the expansion of molecular profiling trials, biological characterization, the study of tumor resistance and immune escape mechanisms—with a particular focus on osteosarcoma—the identification and evaluation of new therapies, and biology-driven clinical trials to validate therapeutic concepts.

Our research benefits from exceptional access to primary tumor samples accompanied by comprehensive clinical annotations and generated multi-omic data, including whole-exome and whole-transcriptome sequencing, single-cell analysis, the national Boost-DataS (EDS) database, patient-derived xenografts and organoids, as well as patients treated with experimental targeted therapies.

To translate biological discoveries into clinical applications, we are pursuing two main lines of research:

1. Identifying therapeutic targets and studying resistance mechanisms in advanced pediatric cancers, with a focus on the biological mechanisms involved in cancer resistance: namely the immune landscape and response mechanisms, DNA repair deficiencies, and metabolism. An in-depth study focuses on osteosarcoma, a disease that is difficult to treat due to its genetic complexity, chromosomal rearrangements, and microenvironment, using single-cell or spatial transcriptomics/proteomics approaches to map tumor plasticity and locate resistant niches.

2. Translate biological discoveries into patient care through the development of biology-driven clinical trials and the identification of biomarkers (e.g., AcSé-ESMART; FOSTER).

Given the underlying complexity of tumors and their hosts, as well as the limitations of preclinical models, we believe that these interactive translational trials are essential to achieving a breakthrough in the implementation of biologically targeted strategies, leading to effective treatments for children with cancer.