title: Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations.
abstract: Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development.
authors.affiliation: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. savita.nandal@novartis.com.
authors.forename: Savita
authors.initials: S
authors.lastname: Nandal
authors.affiliation: Burt Consultancy, 2616 Erwin Rd, Durham, NC 27705, USA. tal.burt@duke.edu.
authors.forename: Tal
authors.initials: T
authors.lastname: Burt
mesh_terms: D015415:Biomarkers; D002986:Clinical Trials as Topic; D019295:Computational Biology / Q000379:methods; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D020543:Proteome; D040901:Proteomics / Q000379:methods
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: Omics; biomarker; clinical development; clinical research; drug development; drug toxicity; early phase development; first-in-human (FIH) studies; pharmacodynamics (PD); pharmacogenomics; pharmacokinetics (PK); pharmacometabolomics; phase 0; phase 1; phase 2; proof-of-concept; proof-of-mechanism; proof-of-principle; proteome; proteomics