Stress and cancer

Tumors are complex cellular systems composed of tumor cells and their microenvironment (TME), which includes immune cells and fibroblasts among the most abundant components. The precise characterization of these different tumor components at time of diagnosis and their evolution during treatment is of interest to avoid metastatic progression and resistance to treatment, main causes of poor patient prognosis. All the mechanisms involved in tumor development, cancer progression and resistance to treatments cannot be explained solely by tumor cells. It is thus important to consider tumors as a whole, including all cellular populations within the TME.

The "Stress and Cancer" laboratory investigates cancer heterogeneity and plasticity, by studying tumors as a whole: analyzing not only tumor cells but also cells of the TME. We are particularly interested in the links between cancer cells and their microenvironment, and their roles in metastatic spread, relapse and resistance to treatments. Thanks to close interactions with clinicians at Institut Curie, notably Dr A. Vincent Salomon at the head of Pathology Department, we analyze patient samples in detail using innovative technologies, including single cell studies, spatial transcriptomics, multiplex immunohistochemistry and tumor-on-chips. Our studies are also based on the development of bioinformatics tools and mathematical modeling allowing extraction, analysis and data integration required for in-depth characterization of patients' tumors.

Through these interdisciplinary projects, we wish to highlight the importance of cellular heterogeneity in cancer progression according to different research programs, which aim to:

• Define the impact of tumor microenvironment heterogeneity and plasticity in different cancer types, including breast, ovarian and lung cancer. We are more specially interested by different populations of Cancer Associated Fibroblasts (CAF) that we discovered, and which are not yet targeted by any treatment, thereby offering a promising therapeutic window in near future.
• Characterize the diversity of tumor cells in cancer through cell metabolism and activation of specific signaling pathways.
• Study the role of heterogeneity of both cancer cells and TME in treatment response.

Our research team, led by Dr Fatima Mechta-Grigoriou, is multidisciplinary, and compose of clinicians, biologists and bioinformaticians. We work in close collaboration with clinicians. Strengthened by numerous collaborations with other teams from the Institut Curie and abroad, we are integrating other specialties, such as mathematics and artificial intelligence, into our studies to go deeper in our research and offer new diagnostic and therapeutic strategies that could benefit patients suffering from cancer.