Abstract

The Unique Challenges and Opportunities of Circulating Tumor DNA

Dan Klass, Principal Scientist, Oncology Assay Development, Roche Sequencing Solutions

Genetic heterogeneity both within and among tumors from different patients serves as a formidable barrier to current cancer therapies, and for most solid tumors the assessment of clinical response to treatment regimens may occur much later than the loss of therapeutic efficacy or the emergence of resistance. Additionally, for the majority of cancers, there are no in vitro diagnostic assays to detect minimal residual disease after definitive therapy. Liquid biopsy has the potential to enable the proactive, personalized future of cancer treatment—but there are several unique technical challenges to the next generation sequencing of circulating tumor DNA (ctDNA). Traditional approaches to sample collection, DNA isolation, library preparation, target enrichment, sequencing, and analysis are often inadequate when faced with the difficulties of liquid biopsy. Emerging workflows combining improved assay efficiency with advanced molecular biology and bioinformatic error suppression methods allow the investigation of new clinical research questions. Early results from these approaches hint that the heralded vision of the future of oncology may be within reach.