Clinical Trials for Precision Oncology Using Next-Generation Sequencing

Richard Simon; Eric Polley


Personalized Medicine. 2013;10(5):485-495. 

In This Article

Abstract and Introduction


The demonstrated genomic heterogeneity of human cancers is having major impacts on the development and evaluation of cancer therapeutics and molecular diagnostics. Many new cancer drugs target somatic alterations in tumors and are being developed with companion diagnostics. Oncology drug development and practice are likely to become increasingly stratified and utilize the enrichment Phase III trial paradigm. Although this paradigm includes an increasing number of successes, single-agent molecularly targeted treatment of metastatic disease will generally provide limited patient benefit. More substantial gains will require better understanding of crosstalk among signaling pathways, ability to combine drugs and use of drugs at initial diagnosis. Early phase discovery clinical trials in which patients will have genome-wide tumor characterization at diagnosis and at critical retreatment points will provide data sets for learning how to effectively match therapeutics to genomic alterations. However, moving tumor genomics to clinical oncology entails many practical challenges. We review some of these challenges and the clinical studies that are being undertaken to translate genomics to clinical oncology.


Large tumor sequencing studies have demonstrated that human cancers of a given histologic type are often heterogeneous with regard to the mutations that drive their invasion and that the mutations present in individual tumors have major influences on the natural history of the tumor, and its responsiveness to therapy. These findings are having a major impact on the development and evaluation of cancer therapeutics and molecular diagnostics. The paradigms for development, evaluation and administration of cancer treatments have been organized around the primary site of the disease and the new findings will have major influence on all levels of oncology research and practice. With this perspective, we will review some new types of clinical studies that are utilizing high-throughput DNA sequencing.