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Rôle de Klotho dans la chimiosensibilisation des liposarcomes dédifférenciés : étude des voies de signalisation impliquées

Abstract : Klotho (KL) is both an anti-ageing and anti-cancer protein. Analysis of clinical data highlights that high expression of KL is associated with a better overall survival of liposarcoma patients. Moreover, its expression in downregulated in dedifferentiated liposarcomas (DDLPS), a rare type of tumor associated with a poor prognosis due to high chemoresistance. Our results show that KL sensitizes DDLPS cells to chemotherapeutic agents (gemcitabine, navitoclax). So, abundance of KL in tumoral tissues could serve as a biomarker for predicting gemcitabine efficacy and so, could help for establishing personalized therapy. Moreover, drugs increasing KL expression could be tested in combination with chemotherapy. Based on KL mechanism of action, we also highlight that the combination between gemcitabine and navitoclax is very effective for killing DDLPS cells.
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Vanessa Delcroix. Rôle de Klotho dans la chimiosensibilisation des liposarcomes dédifférenciés : étude des voies de signalisation impliquées. Médecine humaine et pathologie. Université de Bordeaux, 2017. Français. ⟨NNT : 2017BORD0837⟩. ⟨tel-02399188⟩

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