Advances in metastatic prostate cancer circulating tumor cell enrichment technologies and clinical studies.

Circulating tumor cells (CTCs) have emerged as a pivotal tool that enables molecular interrogation of patient tumor cells and association with clinical outcomes. In prostate cancer specifically, where tumor biopsies from patients with bone metastasis are extremely challenging, CTCs offer a viable and established source of tumor "biopsy". While the prognostic value of CTC enumeration in metastatic prostate cancer is established, there is a compelling need for molecular CTC characterization for effective patient stratification and disease management. The clinical utility of CTCs has been advanced by the evolution of enrichment technologies and their molecular characterization. Enrichment technologies have evolved from strictly EpCAM-based enrichment to antigen-agnostic enrichment, while their clinical utility has evolved from enumeration to advanced downstream analyses including CTC proteomics, transcriptomics and genomics. This chapter offers a comprehensive overview of recent advancements in CTC enrichment and analytical technologies while highlighting pivotal clinical studies in prostate cancer, that utilize CTCs to determine the molecular basis of clinical response and resistance, to assist in disease management and treatment customization.