Joaquin Macheda – Exome-associated miRNAs as circulating biomarkers of chemotherapy resistance in bone tumours (Ewing Sarcoma and Osteosarcoma): Liquid Biopsy and in vitro studies

Objectives

Liquid biopsy is a promising approach to monitor tumour evolution during drug treatment. Circulating nucleic acids might monitor tumour evolution and predict the emergence of resistance. The enrichment of miRNAs in extracellular vesicles (EVs) produced by cancer cells compared to normal cells, coupled with their stability and functional role, entails miRNAs in EVs particularly attractive biomarkers for the early detection and monitoring of cancer. Moreover, miRNAs and other active effectors shuttled by EVs might be directly involved in the escaping mechanisms mastering both tumour microenvironment and distant metastasis. We pursue the identification of blood-borne miRNAs in chemo-resistant osteosarcoma and Ewing sarcoma and the exploration of their functional role.

Expected Results

A panel of circulating miRNAs enriched both in plasma and cell line- derived EVs from chemo resistant osteosarcoma or Ewing sarcoma will be defined. Functional studies allow the prioritization of these miRNAs and we expect to identify which targets/signalling pathways are affected. Overall, we expect to identify a signature that may be applied prospectively to monitor disease progression and we expect to offer novel therapeutic targets.