Massive Parallel Sequencing — Transition from Research to Clinical Testing

Advances in DNA sequencing provide the potential for clinical assays that are timely and affordable and use small amounts of clinicalmaterial. The hypothesis has therefore been raised thatmarked improvements in patient outcomeswill result whenDNAdiagnostics arematched to an armamentariumof targeted agents. While this may be partially true, much of the novel biology uncovered by recent sequencing analysis is poorly understood and not druggable with existing agents. Significant other challenges remain before these technologies can be successfully implemented in the clinic, including the predictive accuracy of pathwaybased models, distinguishing drivers from passenger mutations, development of rational combinations, addressing genomic heterogeneity, and molecular evolution/resistance mechanisms. Developments in regulatory science will also need to proceed in parallel to scientific advances so that targeted treatment approaches can be delivered to small subsets of patients with defined biology and drug reimbursement is available for individuals whose tumor carries a mutation that has been successfully targeted in another malignancy, as long as they agree to participate in an outcome registry. Clin Cancer Res; 19(23); 6371–9.