Dr Urbanucci appointed Group Leader at the Faculty of Medicine and Health Technology (Tampere University, Tampere, Finland)
Dr Urbanucci has been appointed group leader and principal investigator at the Faculty of Medicine and Health Technology (Tampere University, Tampere, Finland) and the new research group website is up: check it out here!
new publication from the lab with contribution from several international collaborators
Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse
We used models of resistance to approved androgen receptor-targeted therapies for prostate cancer to identify subpopulations of treatment-persistent and pre-existing cells. We established that chromatin structure reconfigurations led to alterations in gene expression and drove alternative tumor adaptations and treatment escape. Motivated by the need for pre-treatment biomarkers in prostate cancer, we identified molecular predictors of therapy response based on the presence of treatment-persistent and pre-existing cells.
We show that subpopulations of treatment-persistent cells with stem-like and regenerative properties foster alternative trajectories of enzalutamide resistance in prostate cancer. Alternative transcriptional patterns of resistance are induced by divergent chromatin reprogramming. Transcriptional enrichment of signals from these treatment-persistent cells stratifies patient outcomes in both early stage treatment-naive and treatment-exposed tumors.
Identification of prostate cancer cells with gene expression patterns of regenerative potential that persist and exist prior to enzalutamide treatment.
Profiling of chromatin and transcriptional features from subpopulations of treatment-challenged prostate cancer cells.
Identification of gene signatures associated with stem-like and regenerative potential.
Stratification of prostate cancer patients from “bulk” RNA sequencing data based on identified stemness- and regeneration-related gene signatures.
Approximately 5,000 Norwegian men are diagnosed with prostate cancer each year. Perhaps the most significant clinical challenge today is deciding which type of treatment will work best for different patient groups. In the study "Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse" led by Dr Alfonso Urbanucci from Oslo University Hospital and Professor Matti Nykter from Tampere University, and published in Nature Communications, the researchers found that specific patterns in gene expression and DNA organization can predict patient response to treatment.
Severson TM, Zhu Y, Prekovic S, Schuurman K, Nguyen HM, Brown LG, Hakkola S, Kim Y, Kneppers J, Linder S, Stelloo S, Lieftink C, van der Heijden M, Nykter M, van der Noort V, Sanders J, Morris B, Jenster G, van Leenders GJ, Pomerantz M, Freedman ML, Beijersbergen RL, Urbanucci A, Wessels L, Corey Eet al.(2023) Enhancer profiling identifies epigenetic markers of endocrine resistance and reveals therapeutic options for metastatic castration-resistant prostate cancer patients medRxiv DOI 10.1101/2023.02.24.23286403, PubMed 36865297
Parry MA, Grist E, Mendes L, Dutey-Magni P, Sachdeva A, Brawley C, Murphy L, Proudfoot J, Lall S, Liu Y, Friedrich S, Ismail M, Hoyle A, Ali A, Haran A, Wingate A, Zakka L, Wetterskog D, Amos CL, Atako NB, Wang V, Rush HL, Jones RJ, Leung H, Cross WRet al.(2023) Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial Res Sq DOI 10.21203/rs.3.rs-2488586/v1, PubMed 36798177
Cao S, Wang JR, Ji S, Yang P, Dai Y, Guo S, Montierth MD, Shen JP, Zhao X, Chen J, Lee JJ, Guerrero PA, Spetsieris N, Engedal N, Taavitsainen S, Yu K, Livingstone J, Bhandari V, Hubert SM, Daw NC, Futreal PA, Efstathiou E, Lim B, Viale A, Zhang Jet al.(2022) Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression Nat Biotechnol, 40(11), 1624-1633 DOI 10.1038/s41587-022-01342-x, PubMed 35697807