Prostate cancer is a heterogeneous disease shaped by evolving cellular states within a spatially organized tumor ecosystem. Advances in single-cell RNA-sequencing, single-nucleus sequencing, and spatial transcriptomics have facilitated high-resolution dissection of epithelial lineage hierarchies, tumor-associated luminal states, and microenvironmental remodeling. These approaches have revealed that progression from androgen receptor-dependent adenocarcinoma to castration-resistant prostate cancer and the development of neuroendocrine phenotypes reflect lineage plasticity and epigenetic reprogramming rather than simple linear genetic progression. Single-cell studies have indicated that immunosuppressive niches, cancer-associated fibroblast heterogeneity, endothelial activation, and metabolic adaptation collectively contribute to therapeutic resistance. The integration of multi-omics data with spatial context has begun to redefine prostate cancer taxonomy based on cellular state composition and ecosystem architecture. In this review, we summarize recent discoveries from single-cell and spatial analyses, discuss their implications for biomarker development and treatment stratification, and outline ongoing technical challenges, including standardization, reproducibility, and clinical scalability. Overall, this review provides valuable insights for the development of a state-informed framework to understand prostate cancer progression and guide precision oncology strategies.
American journal of clinical and experimental urology. 2026 Jun 15*** epublish ***
Ryuta Watanabe, Tony Chu, Noriyoshi Miura, Tadahiko Kikugawa, Peter S Nelson, Takashi Saika
Department of Urology, Ehime University Graduate School of Medicine Toon, Japan., Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Center Seattle, WA, USA.