Clinical Pharmacology Analytical CoreExamples
The following are two of many examples of how CPAC has contributed to the development of IUSCC-investigator initiated research - these vignettes are illustrative of how CPAC has helped the IUSCC advance and take the lead in precision prescribing, which refers to the process of matching patients to drugs that will trigger the best response based on an individual's genetic makeup. CPAC has been of critical importance in some noteworthy findings that are described below.
Jamie Renbarger, a clinical pharmacologist and pediatric oncologist, focuses on the pharmacogenetics of vincristine, the most commonly used anticancer agent in children. Her laboratory work resulted in defining the metabolism of vincristine, identification of the structures of its metabolites, and development, in conjunction with the CPAC, of an extremely sensitive assay for measurement of vincristine and its primary metabolite. This work may explain the observed racial disparities in the outcome of childhood cancer treatment and lead to more effective vincristine dosing schemes. As a result of her work with CPAC, Dr Renbarger has received R01, RC1 and U54 grants recently.
Karen Pollok's project, in collaboration with Lindsey Mayo, is focused on utilizing the HDM2 inhibitor, nutlin-3, in treatment strategies for chemotherapy-resistant cancers such as melanoma and glioblastoma. CPAC has developed an assay to effectively measure nutlin-3 in vitro and in vivo – generating strong preliminary data in support of the investigator's hypothesis in their funded R01 application. There is also an ongoing small molecule screen to identify new chemical entity and brain permeable inhibitors of HDM2 for glioblastoma and CPAC is involved in their drug discovery efforts.