Circulating tumor DNA assays in clinical cancer research

Abstract

The importance of circulating free DNA (cfDNA) in cancer clinical research was recognized in 1994 when a mutated RAS gene fragment was detected in a patient's blood sample. Up to 1% of the total circulating DNA in patients with cancer is circulating tumor DNA (ctDNA) that originates from tumor cells. As ctDNA is rapidly cleared from the blood stream and can be obtained byminimally invasivemethods, it can be used as a dynamic cancer biomarker for cancer early detection, diagnosis, and treatmentmonitoring. Despite the potential for clinical use, few ctDNA assays have been cleared or approved by the US Food and Drug Administration. As tools for clinical and translational research, current ctDNA assays face some challenges, andmore research is needed to advance use of these assays. On September 29 30, 2016, the Division of Cancer Treatment and Diagnosis at the National Cancer Institute convened a workshop entitled Circulating Tumor DNA Assays in Clinical Cancer Research to garner input fromindustry experts, academia, and government research and regulatory agencies to understand and promote the translation of ctDNA assays to clinical research, with potential to advance to use in clinical practice. This Commentary presents the topics of the workshop covered in the presentations and pointsmade in the discussions that followed: 1) background on ctDNA, 2) potential clinical utility of ctDNA assays, 3) assay technology, 4) assay clinical and analytical validation, and 5) industry perspectives. Additional relevant information that has come to light since the workshop has been included.