Molecular Targeting in Breast Cancer
Our team uses large-scale genomics, proteomics and bioinformatics to characterize signaling pathways contributing to breast tumorigenesis in cell culture and in vivo tumorigenesis models. We also use molecular modeling combined with structural studies to design novel molecules targeting key proteins. The activity profile of new molecules synthesized by medicinal chemistry as a result of these studies is tested in the experimental models used in the laboratory, which include purification of breast cancer stem cells. Collaborations with clinician scientists, including the Groupe de recherche en cancer du sein (GRCS) of the Centre de recherche du CHUM (CRCHUM), make it possible to translate our basic research into the clinical context in a retrospective or prospective manner.
We have been studying in particular the signaling pathways of nuclear receptors, ligand-dependent transcription factors that are ideal targets for drug development. Dissecting the mechanisms of action of estrogen and retinoic acid receptors has increased our understanding of the mechanisms of chromatin structure and gene transcription regulation by ligands of these receptors, identified transcriptional networks of target genes and clarified their roles in the control of mammary epithelial cell differentiation and proliferation. Our studies have also uncovered the mechanisms of action of drugs currently used for breast cancer treatment, led to the identification of markers of therapeutic success and to the design of novel anti-cancer drugs with improved therapeutic profiles in pre-clinical models.