Deciphering Human Tumor Biology by Single-Cell Expression Profiling

Human tumors are complex ecosystems where diverse cancer and noncancer cells interact to determine tumor biology and response to therapies. Genomic and transcriptomic methods have traditionally profiled these intricate ecosystems as bulk samples, thereby masking individual cellular programs and the variability among them. Recent advances in single-cell profiling have paved the way for studying tumors at the resolution of individual cells, providing a compelling strategy to bridge gaps in our understanding of human tumors. Here, we review methodologies for single-cell expression profiling of tumors and the initial studies deploying them in clinical contexts. We highlight how these studies uncover new biology and provide insights into drug resistance, stem cell programs, metastasis, and tumor classifications. We also discuss areas of technology development in single-cell genomics that provide new tools to address key questions in cancer biology. These emerging studies and technologies have the potential to revolutionize our understanding and management of human malignancies.