Population of Treatment-Resistant Cells Identified in Prostate Cancer Samples

Prostate cancer is the most common male cancer and approximately 5,000 Finnish men are diagnosed with it each year. While most prostate cancers are not aggressive, some tumors develop into a deadly castration-resistant form of the disease. One of the most significant clinical challenges today is deciding which type of treatment will work best for different patient groups with aggressive disease.

In the study “Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse” led by Professor Matti Nykter from Tampere University and Dr. Alfonso Urbanucci from Oslo University Hospital, the researchers identified a specific population of treatment-resistant cells that was present in the study samples prior to treatment and persisted when subjected to treatment.

“By analyzing gene expression patterns and DNA organization in these cells, we were able to predict patient responses to treatment,” says Sinja Taavitsainen, who was responsible for the bioinformatic analysis in the project. “These cells showed stem cell-like and regenerative gene expression patterns,” she continues.

The study utilized a combination of prostate cancer resistance models, some of which were developed at Tampere University by the research groups of Professor Teemu Murtola and Professor Teuvo Tammela, as well as bioinformatics methods to analyze the treatment response to the commonly used drug Xtandi (enzalutamide) at the single-cell level. The results suggest that the presence of treatment-persistent cells in cancer tissue may predict the risk of recurrence and disease development. Such information can help tailor treatment for different subgroups of prostate cancer patients.

“Utilization of state-of-the-art methods including single-cell sequencing of RNA and chromatin state, spatial transcriptomics, and advanced bioinformatics analysis enabled us to analyze the development of treatment resistance in unprecedented detail,” Professor Matti Nykter comments.

Reference: Taavitsainen S, Engedal N, Cao S. et al. Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse. Nat Commun. 2021;12: 5307. doi: 10.1038/s41467-021-25624-1

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