Panaretakis, Theocharis

259 Introduction: RA-223 prolongs OS in BM-CRPC pts but predictive markers are lacking. We hypothesized that molecular profiling of plasma-derived extracellular vesicles (EVs) from BM-CRPC pts treated with RA-223 would predict efficacy and inform development of combinations. Methods: Paired baseline (BL) and end of treatment (EoT) blood samples were collected from 25 pts treated with RA-223. Pts were stratified by median OS into 3 groups: 1) 6.3 months (range 3.3-8.5, n=5 pts, UnFav OS), 2) 18.2 months (range 12.6-19.4, n=7 pts, Middle OS) and 3) 27.6 months (range 23.1-33.8, n=13 pts, Fav OS). EVs were isolated from plasma and analyzed for specific proteins and RNA transcripts. Marker profiles by domain and analytic method were determined in pts from the stratified OS groups. Results: At EoT, there is enrichment of RNA transcripts and proteins involved in regulating immune responses, DNA Damage Response (DDR) and bone metabolism (Table). By benchmarking molecular signatures in pts with UnFav Os and Fav OS, we could analyze the molecular profiles of pts in the Middle OS group and stratify them to UnFav OS or Fav OS groups. Conclusion: Plasma-based molecular markers are predictive for RA-223 efficacy. An association between OS and immune and DDR profiles in men with BM-CRPC may indicate mechanism of action and identify subsets most likely to benefit. These preliminary results provide rationale for combination therapy with RA-223 and immune-checkpoint blockade or PARP inhibition. Clinical trial information: NCT02135484. [Table: see text]

ABSTRACTBioinformatics tools are imperative for the in depth analysis of heterogeneous high‐throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture “what the community needs in a tool”. Here, we describe a novel community‐driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes. Remarkably, with the enthusiastic participation of the community, we were able to implement 90% of the requested features. FunRich enables plugin for extracellular vesicles wherein users can download and analyse data from Vesiclepedia database. By involving researchers early through community needs software development, we believe that comprehensive analysis tools can be developed in various scientific disciplines.