Therapies against metastatic castration-resistant prostate cancer with adenocarcinoma (AdCa) features can induce progression to aggressive neuroendocrine prostate cancer (NEPC). Genomic features underlying AdCa and NEPC have been characterized, but subsequent therapeutic approaches have provided limited efficacy, making clear the importance of factors at nongenomic levels. In their study, Sychev and colleagues explored AdCa and NEPC proteomes and phosphoproteomes using field asymmetric ion mobility spectrometry in AdCa and NEPC patient-derived xenografts (PDX). Unsupervised clustering analysis distinguished AdCa and NEPC samples according to signatures similar to those described at the transcriptomic level. Phosphoproteomic analysis exhibited less heterogeneity, suggesting increased convergence between AdCa and NEPC at that level. Integrated analysis using existing transcriptomic data from the PDX samples revealed significant discordance between RNA expression and corresponding protein abundance. Bioinformatic analysis cross-referencing AdCa- and NEPC-specific hyperabundant proteins with therapeutic target databases identified novel prospective therapeutic targets for both subgroups. Taken together, this study demonstrates...

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