Prostate cancer (PCa) is the first cancer in men with 70,000 new cases, and the second cause of cancer death with almost 8,700 deaths in France each year. While most patients with PCa progress favorably, a significant proportion of them will develop an aggressive disease with the development of metastases. Unfortunately, available treatments control only temporarily the progression of the cancer due to the development of therapeutic resistance. Among the described mechanisms, treatments induce an adaptive response in tumor cells, notably through the emergence of strong tumor phenotypic heterogeneity. This heterogeneity is explained by the ability of tumor cells (epithelial) to transform into other cell types such as neuroendocrine cells or mesenchymal cells. These phenotypic changes contribute to increased cancer heterogeneity, metastasis and resistance to therapies. Our hypothesis is that extracellular vesicles (EVs) play an active role in developing and maintaining this tumor heterogeneity, thereby promoting metastatic process and resistance to treatment. The aim of our research is to study the role of these EVs in the processes involved in prostate tumor cell plasticity. Furthermore, as EVs produced by tumor cells are present in the urine and blood of PCa patients, we also would like to assess their potential as source of biomarkers for predicting PCa and phenotypic tumor heterogeneity in patients in order to better guide treatments.
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