Characterization of extracellular vesicles derived from plasma of mice bearing human renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) represents about 90% of all renal malignancies and their causes are not established until the present moment. Its primary treatment consists of partial or total nephrectomy, but at the time of diagnosis 20% to 30% of the patients present metastasis and another 20% will experience recurrence and metastasis within a period of 1 to 3 years. Treatment for metastatic RCC is based on the use of antiangiogenic agents and mTOR inhibitors. However, the tumor is highly resistant to treatment with a mortality rate above 40%, which indicates the importance of studies in translational medicine that allow the identification of tumor response markers. Patient Derived Xenografts or PDX is an excellent alternative for in vivo study, since it retains the 3D architecture of the original tumors and captures intra and intertumoral heterogeneity. The discovery that extracellular vesicles are able to mediate important processes such as coagulation, immune response and the establishment of pre-metastatic niches have attracted attention for their importance as diagnostic and prognostic markers or as therapeutic targets. In this context, the present project proposes to establish a PDX platform of RCC that allows the development of a methodology for the isolation of vesicles of tumor origin from the plasma of PDX mice that will be submitted to proteomics and genomic approaches for the identification of disease biomarkers. Subsequently, the presence of those biomarkers will be evaluated in the blood of patients with RCC that originated PDXs, in order to correlate their presence with treatment response and prognosis.