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Background: Prostate cancer is the most commonly diagnosed malignancy in the UK. Castrate resistant prostate cancer (CRPC) can be difficult to manage with response to next generation hormonal treatment variable. AR-V7 is a protein biomarker that can be used to predict response to treatment and potentially better inform management in these patients. Our aim was to establish the feasibility of conducting a definitive randomised controlled trial comparing the clinical utility of AR-V7 biomarker assay in personalising treatments for patients with metastatic CRPC within the United Kingdom (UK) National Health Service (NHS). Due to a number of issues the trial was not completed successfully, we aim to discuss and share lessons learned herein. Methods: We conducted a randomised, open, feasibility trial, which aimed to recruit 70 adult men with metastatic CRPC within three secondary care NHS trusts in the UK to be run over an 18-month period. Participants were randomised to personalised treatment based on AR-V7 status (intervention) or standard care (control). The primary outcome was feasibility, which included: recruitment rate, retention and compliance. Additionally, a baseline prevalence of AR-V7 expression was to be estimated. Results: Fourteen participants were screened and 12 randomised with six into each arm over a nine-month period. Reliability issues with the AR-V7 assay meant prevalence was not estimated. Due to limited recruitment the study did not complete to target. Conclusions: Whilst the trial did not complete to target, we have ascertained that men with advanced cancer are willing to take part in trials utilising biomarker guided treatment. A number of issues were identified that serve as important learning points in future clinical trials.

The genome’s structure is highly complex, in relation not only to its sequence but also to its spatial organization and compaction in chromatin around nucleosomal proteins. The degree of chromatin condensation is dynamic, regulated by multiple mechanisms that include covalent histone modifications and nucleosome repositioning. Gene expression, which is inversely related to chromatin compaction, is equally complex, involving regulation by proteins and by increasingly recognized small RNAs such as microRNAs. Gene expression is also affected by single-nucleotide polymorphisms and DNA copy number variants. The combined effects of these factors on gene expression include altered gene transcription, splicing patterns, and translation. The possible biological significance of the extensive regions of noncoding DNA in the genome is currently being investigated. Such data are essential to the interpretation of increasingly available whole genome array and sequencing results, both in research and in the clinical context.