Targeted therapies for cancer have changed treatment approaches for several solid tumor malignancies. Analyses of cell-free (ctDNA) enable noninvasive cancer detection and characterization, prediction of treatment response, monitoring of disease relapse, and identification of mechanisms of resistance to targeted therapies. With newer technologies, the sensitivity and specificity of ctDNA detection assays have improved and facilitate a greater role for ctDNA diagnostics in clinical practice (Figure).

Circulating Quiz Ref ID (cfDNA) was discovered in plasma more than 60 years ago.¹ Several decades later, abnormalities in cfDNA obtained from cancer patients were described and are now known as ctDNA.² Most cfDNA in the circulation is derived from ruptured nonmalignant cells and is of germline origin. ctDNA is thought to be a result of tumor cell apoptosis and necrosis. Analysis of ctDNA can identify tumor-specific DNA abnormalities that can be used as a basis for highly specific disease testing strategies. Detecting the small amount of tumor-derived mutations in cfDNA has been a major limitation in the clinical application of ctDNA testing. Recently developed novel genomic and bioinformatic approaches have facilitated highly sensitive molecular assays that can detect tumor-specific aberrations from ctDNA.^3-5