Pharmacology Shared Resource

PHARMACOLOGY SHARED RESOURCE REPORT PROJECT SUMMARY The Pharmacology Shared Resource (PHM) has been an important component and a high priority area of emphasis for the development and evaluation of new agents and for the treatment of malignant diseases within the Mayo Clinic Cancer Center (MCCC) for many years. More than 35 years ago, the MCCC initiated a major effort to establish cancer pharmacology and experimental therapeutics expertise in order to enhance and strengthen clinical trials and related research in the Cancer Center. Along with establishment of the Experimental Therapeutics Program, the other major addition to the Cancer Center in this regard was the PHM, developed initially to provide clinical pharmacology expertise and services in support of NCI-funded Phase I clinical trials. As the clinical and translational components of the MCCC have grown, so has the importance of this resource to MCCC members. The PHM provides clinical pharmacologic expertise, methodologies, services and support to MCCC members that have been key to the success of the PHM since its inception. In addition to the clinical pharmacology support, the PHM provides consultative services and pharmacologic support to clinician investigators who do not have their own laboratory programs; basic scientists collecting preliminary pharmacologic data for grant applications; and investigators who have pharmacologic aims in their grants or wish to pursue leads with potentially druggable targets. Expertise and services to meet that demand include the development and implementation of robust analytical methodologies to measure drugs and metabolites in biological matrices; detailed methods to study drug metabolism and identify metabolites; modelling and simulation software for pharmacokinetic and pharmacodynamics analysis; the development and implementation of pharmacogenetic methodologies to assess the role of genetic variation in the individualized response to chemotherapeutic agents; and basic pharmacologic methodologies to support MCCC investigator-initiated research. The PHM Director, laboratory personnel and research nurse all have >20 years of experience in conducting pharmacologic investigations. The PHM is fully equipped to carry out pharmacologic investigations including 3 triple quadrupole mass spectrometers and a quantitative time of flight (QTOF) mass spectrometer, each with Accuity UPLC modules. The PHM also has fully equipped facilities for animal procedures, cell culture and PCR. We maintain annual licenses for several programs used for pharmacokinetic and pharmacodynamics analysis including WINNONLIN, NONMEM, Simcyp, and PKSim. By providing a single source and forum for expertise in pharmacologic aspects of preclinical and clinical trials research to MCCC members, the PHM fosters integrated pharmacologic research in MCCC Programs.