LYOS – INSERM U1033,
Team «Bone, Cancers and Metastases»,
Université de Lyon, France.
Bone metastases, the spread of cancer to the bones, occur in more than 1.5 million patients with cancer world-wide. Conventional therapeutics are only palliative. Thus, it is of vital importance to identify molecular mechanisms that precede the overt development of skeletal lesions in order to find effective molecularly-targeted therapies.
Our projects aim at studying the role of some specific matrix enzymes (lysyl oxidases), receptors (ROBO, ERR, RANK) and their regulators (microRNAs) in the fate of circulating cancer cells after they have extravasated, seeded and adapted (osteomimetism) in the bone marrow. By means of gene (and miRNA) silencing and/or overexpression strategies, in-vitro cell-based assays and in-vivo models of dissemination and metastasis, we will investigate the functions of these factors and their regulators in the colonization of the bone marrow by cancer cells. Blood-based miRNAs have received considerable research interest as biomarkers in cancer. We will identify circulating miRNA biomarkers that are predictive of bone metastasis from the serum of patients with early-stage cancer. Another major challenge is the identification of patients with bone metastasis at high risk of developing pathological fractures. The Mirel score is the current standard to guide surgical decision. We will set up a numerical model by finite element analysis (FEA) to predict pathological fractures associated to bone metastasis.
These projects are funded by grants obtained from INSERM, the University of Lyon-1, highly selective national research programs [the laboratory of excellence LabEx DEVweCAN, the national cancer institute (INCa) project ARROW], charities (Ligue contre le Cancer, Association Cancer du Sein, Parlons-en!, Fondation de France) and two European Marie Curie projects: the Initial Training Network BONE-NET and the Individual Fellowship MIROMES.