Single-cell sequencing (SCS) is a powerful new tool that applies Next Generation Sequencing at the cellular level. SCS has revolutionized our understanding of
tumor heterogeneity and the tumor microenvironment, immune infiltration, cancer stem cells (CSCs),
circulating tumor cells (CTCs), and clonal evolution. The following chapter highlights the current literature on SCS in genitourinary (GU)
malignancies and discusses future applications of SCS technology. The
renal cell carcinoma (RCC) section highlights the use of SCS in characterizing the initial cells driving
tumorigenesis, the intercellular mutational landscape of RCC, intratumoral heterogeneity (ITH) between primary and metastatic lesions, and genes driving RCC cancer stem cells (CSCs). The
bladder cancer section will also illustrate molecular drivers of
bladder cancer stem cells (BCSCs), SCS use in reconstructing
tumor developmental history and underlying subclones, and understanding the effect of
cisplatin on intratumoral heterogeneity in vitro and potential mechanisms behind
platinum resistance. The final section featuring
prostate cancer will discuss how SCS can be used to identify the cellular origins of
benign prostatic hyperplasia and
prostate cancer, the plasticity and heterogeneity of
prostate cancer cells with regard to
androgen dependence, and the use of SCS in CTCs to understand
chemotherapy resistance and gene expression changes after
androgen deprivation
therapy (ADT). The studies listed in this chapter illustrate many translational applications of SCS in GU
malignancies, including diagnostic, prognostic, and treatment-related approaches. The ability of SCS to resolve intratumor heterogeneity and better define the genomic landscape of
tumors and CTCs will be fundamental in the new era of precision-based care.