Circulating Tumor Cells as Biomarkers for Renal Cell Carcinoma: Ready for Prime Time?

SIMPLE SUMMARY: Renal cell carcinoma (RCC) is the most common form of kidney cancer, characterized by silent progression at early stages, heterogeneous behavior and resistance to chemotherapy and radiotherapy. The clinical challenges posed by RCC require the development of a novel class of biomarkers which may better portray the biology of the disease. Herein, we explore the potential of circulating tumor cells (CTCs) as a source of biomarker information in RCC, emphasizing the more recently published findings, highlighting CTCs biology and molecular characterization through existing and emerging techniques for CTC enrichment and detection, exploring their clinical applications in RCC. ABSTRACT: Renal cell carcinoma (RCC) is among the 15 most common cancers worldwide, with rising incidence. In most cases, this is a silent disease until it reaches advance stages, demanding new effective biomarkers in all domains, from detection to post-therapy monitoring. Circulating tumor cells (CTC) have the potential to provide minimally invasive information to guide assessment of the disease’s aggressiveness and therapeutic strategy, representing a special pool of neoplastic cells which bear metastatic potential. In some tumor models, CTCs’ enumeration has been associated with prognosis, but there is a largely unexplored potential for clinical applicability encompassing screening, diagnosis, early detection of metastases, prognosis, response to therapy and monitoring. Nonetheless, lack of standardization and high cost hinder the translation into clinical practice. Thus, new methods for collection and analysis (genomic, proteomic, transcriptomic, epigenomic and metabolomic) are needed to ascertain the role of CTC as a RCC biomarker. Herein, we provide a critical overview of the most recently published data on the role and clinical potential of CTCs in RCC, addressing their biology and the molecular characterization of this remarkable set of tumor cells. Furthermore, we highlight the existing and emerging techniques for CTC enrichment and detection, exploring clinical applications in RCC. Notwithstanding the notable progress in recent years, the use of CTCs in a routine clinical scenario of RCC patients requires further research and technological development, enabling multimodal analysis to take advantage of the wealth of information they provide.