Abstract
Much has been written about the promise of "precision medicine," especially in oncology, where somatic mutations can influence the response of cancer cells to "targeted therapy." There have been successful examples of targeted therapy improving the outcome of some childhood cancers, such as the addition of an ABL class tyrosine kinase inhibitor to conventional chemotherapy substantially improving the cure rate for patients with BCR-ABL1 positive acute lymphoblastic leukemia. Although there are other mutations serving as putative targets in various childhood leukemias and solid tumors, effective targeted therapy has yet to be established for them in prospective clinical trials. There are also uncertainties about which "targeted therapy" to use when patients have multiple targetable genomic lesions in their cancer cells, given the paucity of data upon which to develop evidence-based guidelines for selecting and integrating targeted agents for individual patients. There are also multiple examples of inherited germline variants for which evidence-based guidelines have been developed by the Clinical Pharmacogenetics Implementation Consortium to guide the selection and dosing of medications in children with cancer. Clinical pharmacology is poised to play a critical role in both the discovery and development of new targeted anticancer agents and their evidence-based translation into better treatment for children with cancer. To embrace these challenges and opportunities of "precision medicine," clinical and basic pharmacologists must expand the depth of our science and the bandwidth of our translational capacity if we are to optimize precision medicine and advance the treatment of cancer in children and adults.