16 Chapter 1 Transrenal excretion of cfDNA Local shedding of cell fragments Tumor cell Normal cell-free DNA Tumor cell-free DNA Normal cell Full void urine Urine sediment Urine supernatant Low molecular weight DNA High molecular weight DNA Figure 3: Urine as a liquid biopsy for cancer detection. Urine consists of different components, including normal and tumor-derived cell-free DNA and cellular debris from both normal and tumor cells. Cell-free DNA is transported into the urine by transrenal excretion. The anatomical position of the cervix and bladder allows the local shedding of cells and DNA into the urine. Created with BioRender.com. 1.5 Urine-based biomarker testing to address clinical challenges of different cancer types Given the advantages of urine collection, urine-based tests could address a wide range of clinical challenges in cancer management. Patient-friendly testing has been developed and evaluated for the accurate detection of cervical (pre)cancer in urine and cervicovaginal self-samples (22, 70). Yet, the application of urine and cervicovaginal self-samples for the detection of other gynecological cancers, including endometrial and ovarian cancer, has remained underexplored. Furthermore, although detecting non-urogenital tract cancer types in urine is appealing, this has only been examined by a limited number of studies (8). The use of urine for lung cancer detection has been described previously but focused on late-stage disease (73, 74). The feasibility of detecting early-stage lung cancer in urine, which is clinically most relevant, is largely unknown. The cancer types examined in this thesis originate from different sites of the human body and have distinct clinical challenges, which are described in the subsections below (Figure 4).
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