The discovery that cancer cells release their content into the bloodstream has opened vast opportunities for characterizing cancer without the need for invasive procedures, as a simple blood draw can now detect and analyze cancer cells. While circulating DNA molecules have long been used, extracellular RNA (cell-free RNA, exRNA) has recently emerged as a promising analyte. To advance the exRNA research field and deliver innovations in biomarker research with the ultimate goal of improving cancer patients’ outcomes, my research addresses important open questions on the biology of tumor-derived exRNA in liquid biopsies. Key aspects include investigating how tumor burden impacts tumor exRNA detection sensitivity, how exRNA levels evolve during disease course, treatment and follow-up, how and to what extent tumor-derived exRNAs are protected from degradation in the blood, and what their half-lives are in circulation. Sequencing-based technologies are applied to profile liquid biopsies from cancer xenograft models and patients.