ArticleNature communications2015
Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer.
Registry-linked trialAbstract read
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Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04015622 (A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone), which is not on this map. Cited by 208 papers.
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208citing papers in PubMed
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
NCT04015622 phase2active not recruitingnot on this mapstarted 2020, after this paper: background citation
A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone
Who cites it
208 citing papers in PubMed.
- Olaparib Efficacy in Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1, BRCA2, or ATM Alterations Identified by Testing Circulating Tumor DNA.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Molecular Profiling-Based Assignment of Cancer Therapy (NCI-MPACT): A Randomized Multicenter Phase II Trial.JCO precision oncology · 2021Trial
- Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer.The Journal of clinical investigation · 2020Trial
- Clinical metastatic cancer from initiation to colonization: emerging challenges and breakthroughs.Oncogene · 2026Review
- Uncovering genes driving developmental stage progression in prostate cancer through spatial transcriptomics.Genes & diseases · 2026Article
- Coupled Cell-Intrinsic and Microenvironmental Heterogeneity Drives Divergent Trajectories in Castration-Resistant Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Transient centrosome loss in cultured prostate epithelial cells induces chromosomal instability to produce an oncogenic genotype that correlates with poor clinical outcomes.British journal of cancer · 2026Article
- Exploring the biology of metastatic hormone-sensitive prostate cancer: on the road to precision medicine.The Journal of clinical investigation · 2026Review
- Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution.International journal of cancer · 2026Review
- Uncovering the role of ETS2 in prostate cancer pathogenesis: relationship with p53 and ERG.Molecular biology reports · 2026Article
- Clonal evolution and transcriptional plasticity shape metastatic dissemination routes in prostate cancer.Nature communications · 2025Article
- Blood-Based Genomic Alteration Signature for Predicting Progression-Free Survival in De Novo Metastatic Hormone-Sensitive Prostate Cancer: A Real-World Study.Cancer research communications · 2025Article
- Divergent Clonal Evolution and Early Dissemination Promote Genetic Heterogeneity of Metastases in Castration-Resistant Prostate Cancer.Cancer research · 2025Article
- Tracing metastatic spread in pediatric solid tumors using copy number and targeted deep sequencing.The Journal of pathology · 2025Article
- Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications.Cancer cell · 2025Review
- Patterns of intra- and intertumor phenotypic heterogeneity in lethal prostate cancer.The Journal of clinical investigation · 2025Article
- Precision Targeting in Metastatic Prostate Cancer: Molecular Insights to Therapeutic Frontiers.Biomolecules · 2025Review
- Molecular Underpinnings of Brain Metastases.International journal of molecular sciences · 2025Review
- Review
- Heterogeneity in Cancer.Cancers · 2025Review
148 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors.
Matthew K H Hong1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
Geoff Macintyre1] Centre for Neural Engineering, Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia [2] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [3] Diagnostic Genomics, NICTA, Victoria Research Laboratory, The University of Melbourne, Parkville, Victoria 3010, Australia.
David C WedgeCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Peter Van Loo1] Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Department of Human Genetics, KU Leuven, Herestraat 49 Box 602, B-3000 Leuven, Belgium [3] Cancer Research UK London Research Institute, London WC2A 3LY, UK.ORCID 0000000302921949
Keval Patel1] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [2] Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK.
Sebastian LunkeCentre for Translational Pathology, University of Melbourne, Parkville 3050, Victoria, Australia.
Ludmil B Alexandrov1] Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.ORCID 0000000335964515
Clare SloggettVictorian Life Sciences Computation Initiative, The University of Melbourne, Parkville 3050, Victoria, Australia.
Marek Cmero1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia [3] Centre for Neural Engineering, Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia [4] Diagnostic Genomics, NICTA, Victoria Research Laboratory, The University of Melbourne, Parkville, Victoria 3010, Australia.
Francesco MarassCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Dana TsuiCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Stefano MangiolaCentre for Neural Engineering, Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
Andrew LonieVictorian Life Sciences Computation Initiative, The University of Melbourne, Parkville 3050, Victoria, Australia.
Haroon Naeem1] Centre for Neural Engineering, Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia [2] Diagnostic Genomics, NICTA, Victoria Research Laboratory, The University of Melbourne, Parkville, Victoria 3010, Australia.
Nikhil Sapre1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
Pramit M PhalDepartment of Radiology, Royal Melbourne Hospital, Parkville 3050, Victoria, Australia.
Natalie Kurganovs1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
Xiaowen Chin1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
Michael Kerger1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.ORCID 000000029745728X
Anne Y WarrenDepartment of Histopathology, University Cambridge Hospitals, Addenbrookes Hospital, Hills Road, Cambridge CB2 0QQ, UK.
David Neal1] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [2] Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK.
Vincent Gnanapragasam1] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [2] Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK.
Nitzan RosenfeldCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
John S Pedersen1] TissuPath Specialist Pathology, Mount Waverley 3149, Victoria, Australia [2] Monash University Faculty of Medicine, Clayton 3168, Victoria, Australia.
Andrew RyanTissuPath Specialist Pathology, Mount Waverley 3149, Victoria, Australia.
Izhak HavivBar-Ilan University Medical School, Safad 1311502, Israel.
Anthony J Costello1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
Niall M Corcoran1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
Christopher M Hovens1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
Funding
Cancer Research UK 20240Cancer Research UK C14303/A17197
Abstract
Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.
Indexed as
AdenocarcinomaAgedBone NeoplasmsBrain NeoplasmsDisease ProgressionDNA Copy Number VariationsHumansLongitudinal StudiesMaleMiddle AgedMutationNeoplasm MetastasisPolymorphism, Single NucleotideProstatic NeoplasmsRNA, MessengerSequence Analysis, DNARNA, MessengerTP53 protein, humanTumor Suppressor Protein p53
Identifiers
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LicenceCC BY
Read underepoch 390
Registered trials
NCT04015622ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.