MOLECULAR PHARMACOLOGY SHARED RESOURCE (MPSR) PROJECT SUMMARY/ABSTRACT The Molecular Pharmacology Shared Resource (MPSR) at the UC Davis Comprehensive Cancer Center (UCDCCC) has centralized services to conduct clinical pharmacokinetic (PK)/pharmacodynamic (PD) studies and preclinical modeling of new therapeutics. Understanding PK/PD properties of individual drugs is essential for preclinical and clinical drug development, as well as clinical practice of precision medicine in cancer. Many clinical studies conducted at the UCDCCC, including investigator-initiated clinical trials (IIT) or National Cancer Institute (NCI)-funded Experimental Therapeutics Clinical Trials Network (ETCTN) trails, and the National Clinical Trials Network (NCTN) trials for which UCDCCC is a Lead Academic Participating Site, involve the assessment of PK/PD properties and on-target pharmacological actions. Meanwhile, defining drug metabolism (DM) and PK/PD characteristics in appropriate preclinical models is vital before translating new therapeutic drugs into clinical investigations. The MPSR provides comprehensive services for high-quality collection, processing and analysis of clinical specimens from trial patients to assess clinical PK/PD, and preclinical assessment of novel therapeutics and regimens, including DM/PK/PD, on-target mechanisms, biomarkers, drug-drug interactions (DDI) and combination effects. In addition, the MPSR provides support for IITs by helping with protocol and assay development. Very recent acquisition of a state-of-the-art, live-cell metabolic assay platform, the Seahorse XFe Analyzer, will further strengthen basic and translational research in the areas of cancer metabolism at UCDCCC. Oversight and management of the MPSR is provided by the Director, Aiming Yu, PhD, a world leader in the fields of DM/PK, studying molecular mechanisms of DM/PK/PD and anticancer pharmacology, and the Technical Manager, Anthony Martinez, BS, the Assistant Director of the Office of Clinical Research (OCR), with over 7 years' experience in clinical trials and 20 years' in cancer research. The Specific Aims for the MPSR are: 1) Clinical Trial Specimen Management, in which the MPSR oversees biospecimens collection, processing and storage for patients enrolled on clinical trials conducted at UCDCCC; 2) Protocol Development and Clinical PK/PD studies, in which the MPSR supports study design, and protocol development, develops new in-house assays and conducts targeted analyses of drugs, metabolites and biomarkers, performs PK/PD data analysis and interpretation; and 3) Preclinical Modeling in which the MPSR evaluates new agents and treatments for precision medicine that are translatable to the clinic.