Drug monitoring in saliva combined with pharmacogenomics allows unprecedented opportunity to monitor and investigate drug metabolism as it relates to toxicity in children. In childhood cancers, toxicity ranges from myelosuppression to chronic central and peripheral nervous deficits and cardiomyopathy that can be lifelong and progressive. At least one contributing factor to chemotherapeutic toxicity is the inability to monitor and balance drug levels with therapeutic effects versus toxicity. If saliv could be optimized to as a matrix for drug monitoring, the safety profile of chemotherapy would be improved by enabling more frequent, noninvasive sampling. To develop saliva as an optimal repository matrix, this research will optimize saliva collection, stabilization, processing, storag, and assay protocols thereby creating the first pediatric saliva biorepository dedicated to the study of chemotherapy in children. This research will be segmented into 3 specific aims including: (1) refining collection, stabilization, processing, and storage for drug and metabolite analysis in (spiked) saliva from children not treated with doxorubicin and (2) validating those saliva methods against the gold standard blood matrix in doxorubicin-treated children, and, (3) determining the feasibility of pharmacogenomics analysis in children with cancer using DNA isolated from cryopreserved saliva. Increasing the saliva stability will enable future studies on the feasibility and utility of home-based saliva collection for drug level monitoring in children. Thus, our overall goal is to refine, design, and develop the techniques and procedures needed to stabilize saliva for drug analysis with the future goal of home drug monitoring kit to ensure therapy compliance and to establish the first saliva biorepository for drug monitoring in childhood cancers.
The overall goal of this proposal is to establish a saliva biorepository in childhood cancer patients in order to refine the techniques and procedures needed to stabilize and store saliva for drug monitoring and pharmacogenetic analysis. If these methods are validated, they could provide benchmarks for drug monitoring for future investigational interventions and could contribute to the reduction of toxic outcomes.
