Cancer genomics meets clinical trials: the challenge ahead.

targets, to facilitate molecular eligibility for a c omplement of innovative clinical trials. Several strategies have emerged to character ize the hundreds or thousands of genetic mutations in an individual cancer using next-generation sequencing [4–7]. While each of these approaches has distinct advantages, they all must consider key barriers for clinical translation, including turnaround time for testing, good laboratory practices (Clinical Laboratory Improvements Amendment [CLIA] certification), US FDA regulations for diagnostic testing, cost and interpretation of results. For practical application, initial turnaround time of 2–4 weeks is reasonable, as patients usually have a ‘washout’ period for prior therapies before participating in another trial. As technology permits, laboratories will soon be able to provide results within 1 week, which will facilitate greater use of testing and application for clinical trial eligibility and enrollment. The CLIA sets and enforces minimum laboratory standards to ensure that diagnostic laboratories produce reliable results that can be utilized for clinical decision-making. Both developers of cancer gene panels and instruments have considered CLIA certification and this is already in place at some institutions and companies. Recently, the Institute of Medicine (DC, USA) charged a committee with out lining principles for developing and translating ’omics-based tests for clinical trials [101]. In addition to CLIA certification, the underlying theme of the report was to promote transparency for methods, analysis and reporting. With respect to next-generation sequencing, this will entail standardization of vetted computational methods for a given molecular diagnostic test. Once the infrastructure for expedited CLIA certified testing is in place, the ensuing question is how to design a clinical trial to test putative biomarkers. The American Association for Cancer Recent advances in DNA sequencing have facilitated the characterization of cancer genomes through large-scale genome projects. There is potential to apply these technologies for individual patients with cancer who are considering clinical trials. A 2011 report by the National Academy of Sciences (DC, USA) promoted an approach called ‘precision medicine’ through the develop ment of a molecular taxonomy for human diseases [1]. Cancer is a disease of acquired genetic and epigenetic aberrations, and so it is an ideal model for developing precision medicine through genomic strategies. Furthermore, the majority of cancer drugs in development are molecularly targeted therapies with matching genomic targets, such as kinases and cell-surface receptors. In this article, I advocate application of DNA sequencing tech nologies as a broad molecular diagnostic tool to enrich patients for clinical trials of molecularly targeted therapies. To fully leverage DNA sequencing technologies for targeted therapy development, there are two parallel networks that must be linked. First, an infrastructure for real-time molecular characterization of cancer must be created, and second, trials must be implemented to leverage these technologies for putative genomic targets. Recently, two high-profile trials have illustrated the potential impact of this approach, targeting the BRAF V600E/K activating mutation in melanoma and ALK gene fusions in lung cancer [2,3]. To molecularly enrich these trials, investigators screened hundreds of potential patients through single-gene assays for the presence of a BRAF mutation or ALK gene fusion. This single gene approach left many patients without actionable data and no direction for other molecularly directed therapies. Alternatively, one can envision academic cancer centers employing a universal profiling strategy for all patients with advanced cancer, screening for multiple