Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond to systemic therapy. Here, we employ single-cell assays for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide.
In doing so, we identify pre-existing and treatment-persistent cell subpopulations that possess regenerative potential when subjected to treatment. We find distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent cells are able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal as yet unrecognized molecular predictors of treatment response. This suggests that the application of single-cell methods with high analytical resolution in pre-clinical models may powerfully inform clinical decision-making.
Nature communications. 2021 Sep 06*** epublish ***
S Taavitsainen, N Engedal, S Cao, F Handle, A Erickson, S Prekovic, D Wetterskog, T Tolonen, E M Vuorinen, A Kiviaho, R Nätkin, T Häkkinen, W Devlies, S Henttinen, R Kaarijärvi, M Lahnalampi, H Kaljunen, K Nowakowska, H Syvälä, M Bläuer, P Cremaschi, F Claessens, T Visakorpi, T L J Tammela, T Murtola, K J Granberg, A D Lamb, K Ketola, I G Mills, G Attard, W Wang, M Nykter, A Urbanucci
Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland., Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium., Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., University College London Cancer Institute, London, UK., Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland., Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland. ., Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/34489465