Clinical Trials in the Genomic Era.

Personalization of therapy to target specific molecular pathways has been placed in the forefront of cancer research. Initial reports from clinical trials designed to select patients for appropriate treatment on the basis of tumor characteristics not only have generated considerable excitement but also have identified several challenges. These challenges include the overcoming of regulatory and logistic difficulties, identification of the best selection biomarkers and diagnostic platforms that can be applied in the clinical setting, definition of relevant outcomes in small preselected patient populations, and the design of methods that facilitate rapid enrollment and interpretation of clinical trials by aggregating data across histologically diverse malignancies with common genetic alterations. Furthermore, because our knowledge of the functional consequences of many genetic alterations lags, investigators and sponsors struggle with choosing between ideal clinical trial designs and more practical ones. These challenges are amplified when more than one biomarker is used to select patients for a combination of targeted agents. This review summarizes the current status and challenges of clinical trials in the genomic era and proposes ways to address these challenges.