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RESEARCH PRODUCT

HSP70-exosomes for the monitoring of cancer

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Actually, cancer is unfortunately part of our daily life. Although it is better treated, more and more people are affected. Cancer research is working on two side: therapy and diagnosis. The next-generation therapies show wonderful results that were never reached so far, but diagnosis improvement can also save lives. It is well established that the earlier the cancer is diagnosed, the better the survival rate. Idem for the follow-up of the disease. In this context of precision and earliness, liquid biopsy spark interest and seems to have a bright future. It consists in the investigation of liquid analytes, particularly within the bloodstream, such as circulating tumor DNA, circulating tumor cells (CTCs) and exosomes.This manuscript aims to put my research work on exosomes in the context of liquid biopsy, in order to let you compare with other analytes and understand their diagnosis potential. Exosomes are nanovesicles released by all cells that can be found in the blood. They carry genetic material, proteins end lipids. A key point for their use as potential biomarkers in cancer is to differentiate tumor-derived exosomes from other circulating nanovesicles.Heat shock protein-70 (HSP70) has been shown to be abundantly expressed by cancer cells and to be associated with bad prognosis. We previously showed that exosomes derived from cancer cells carried HSP70 in the membrane while those from non- cancerous cells did not. In this work, we opened a prospective clinical pilot study including breast and lung cancer patients to determine whether it was possible to detect and quantify HSP70 exosomes in the blood of patients with solid cancers.We found that circulating exosomal HSP70 levels, but not soluble HSP70, reflected HSP70 content within the tumour biopsies. Circulating HSP70 exosomes increased in metastatic patients compared to non-metastatic patients or healthy volunteers. Further, we demonstrated that HSP70-exosome levels correlated with the disease status and, when compared with circulating tumor cells, were more sensitive tumor dissemination predictors. Finally, our case studies indicated that HSP70-exosome levels inversely correlated with response to the therapy and that, therefore, monitoring changes in circulating exosomal HSP70 might be useful to predict tumor response and clinical outcome.