Abstract
Liquid biopsy profiling of circulating tumor DNA (ctDNA) has become established as a compelling, pragmatic diagnostic in the care of cancer patients and is now endorsed by multiple cancer care guidelines. Moreover, ctDNA profiling technologies have advanced significantly and offer increasingly comprehensive and reliable insights into cancer. In this review, we focus on applications of ctDNA and propose that a critical untapped opportunity is in considering how we utilize these accessible, scalable technologies across diverse potential applications. With a specific focus on clinical applications, rather than research uses, we describe 10 use cases for ctDNA profiling across four categories: (1) established and (2) emerging applications of ctDNA profiling for therapy selection, (3) incidental detection of secondary genomic findings, and (4) quantification of plasma DNA tumor content.