Role of tumor cell metabolic plasticity in resistance to chemotherapy in ovarian cancer – MetaboInOV

Ovarian epithelial cancer is one of the deadliest forms of gynecological cancer. Despite the development of therapeutic strategies combining surgery, chemotherapy and targeted therapies, many patients relapse and often have few therapeutic alternatives. Metabo'InOV proposes an innovative approach to better understand the molecular mechanisms involved in chemotherapy resistance by precisely characterizing the cancer cells in the residual disease.
Our preliminary data demonstrate a mesenchymal phenotypic change associated with a metabolic switch after chemotherapy. Furthermore, our single-cell transcriptomic analyses reveal that certain subpopulations of tumor cells, identified at diagnosis, accumulate preferentially after chemotherapy in residual tumor samples. Interestingly, a fraction of these residual cells displays both epithelial and mesenchymal characteristics, which may indicate a cell plasticity and a bidirectional interconversion state.

Our project aims to deeply characterize the metabolic and identity plasticity of these residual cells from diagnosis, post-treatment and to the relapse in order to better understand the mechanisms of resistance to chemotherapy. We propose an innovative combination of metabolomic, transcriptomic and epigenetic approaches to:
WP1: Investigate the metabolic and cell identity features of residual ovarian cancer cells
WP2: Identify the epigenetic mechanisms regulating the residual state in HGSOC
WP3: Targeting chemotherapy-induced metabolic reprogramming to suppress residual cells

The achievement of Metabo'InOV will contribute to a better understanding of cellular plasticity and metabolic reprogramming induced by chemotherapy in ovarian cancers, with the ultimate objective of identifying novel therapeutic targets.