Single-Cell Transcriptomics Sheds Light on Tumor Evolution: Perspectives from City of Hope’s Clinical Trial Teams

Tumor heterogeneity is a significant factor influencing cancer treatment effectiveness and can arise from genetic, epigenetic, and phenotypic variations among cancer cells. Understanding how tumor heterogeneity impacts tumor evolution and therapy response can lead to more effective treatments and improved patient outcomes. Traditional bulk genomic approaches fail to provide insights into cellular-level events, whereas single-cell RNA sequencing (scRNA-seq) offers transcriptomic analysis at the individual cell level, advancing our understanding of tumor growth, progression, and drug response. However, implementing single-cell approaches in clinical trials involves challenges, such as obtaining high-quality cells, technical variability, and the need for complex computational analysis. Effective implementation of single-cell genomics in clinical trials requires a collaborative "Team Medicine" approach, leveraging shared resources, expertise, and workflows. Here, we describe key technical considerations in implementing the collection of research biopsies and lessons learned from integrating scRNA-seq into City of Hope's clinical trial design, highlighting collaborative efforts between computational and clinical teams across breast, brain, and ovarian cancer studies to understand the composition, phenotypic state, and underlying resistance mechanisms within the tumor microenvironment.