Single-cell analyses to tailor treatments

Alex K. Shalek and Mikael Benson.

Single-cell RNA-seq could play a key role in personalized medicine by facilitating characterization of cells, pathways, and genes associated with human diseases such as cancer.

We discuss the potential of single-cell RNA sequencing (scRNA-seq) to empower clinical implementation of personalized medicine. On the basis of work to date, we emphasize applications in cancer. Nevertheless, the underlying problems and solutions should be generally applicable to other complex diseases. One of health care’s largest outstanding issues is that many patients do not respond to treatment. By recent estimates, about 90% of drugs are effective for less than 50% of patients. This causes enormous physical, social, and economic suffering. The annual cost of ineffective treatment is estimated at $350 billion/year in the United States alone. Moreover, variable treatment response contributes to the rising cost of drug development, currently around $2.6 billion per drug. A fundamental driver of these inefficiencies is the cellular heterogeneity that exists within and between patients in cancer and other complex diseases, which can involve altered behaviors across multiple cell types and hundreds of genes. To date, such changes have often been profiled at the population level. This can mask intercellular variations that can be functionally and clinically relevant. For instance, in cancer, treatment failure may result if a tumor contains many malignant subsets, of which only some respond to treatment.


Sci Transl Med 9, eaan4730.