Renal cell carcinoma is a highly malignant cancer that would benefit from non-invasive innovative markers providing early diagnosis and recurrence detection. Circulating tumor cells are a particularly promising marker of tumor invasion that could be used to improve the management of patients with RCC. However, the extensive genetic and immunophenotypic heterogeneity of cells from RCC and their trend to transition to the mesenchymal phenotype when they circulate in blood constitute a challenge for their sensitive and specific detection. This review analyzes published studies targeting CTC in patients with RCC, in the context of the biological, pathological, and molecular complexity of this particular cancer. Although further analytical and clinical studies are needed to pinpoint the most suitable approach for highly sensitive CTC detection in RCC patients, it is clear that this field can bring a relevant guide to clinicians and help to RCC patients. Furthermore, as described, a particular subtype of RCC-the ccRCC-can be used as a model to study the relationship between cytomorphological and genetic cellular markers of malignancy, an important issue for the study of CTC from any type of solid cancer.
Keywords: Isolation by Size of Tumor cells (ISET); circulating cancer cells (CCC); circulating tumor cells (CTC); clear cell renal cell carcinoma (ccRCC); liquid biopsy.