Detecting liquid remnants of solid tumors treated with curative intent: Circulating tumor DNA as a biomarker of minimal residual disease (Review)

Abstract

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker of minimal residual disease (MRD) in solid tumors. There is increasing evidence to suggest that the detection of ctDNA following curative-intent treatments has high potential in anticipating future relapse in various solid tumors. Multiple liquid biopsy technical approaches and commercial platforms, including tumor-informed and tumor-agnostic ctDNA assays, have been developed for ctDNA-based MRD detection in solid tumors. Accurate ctDNA-based MRD analysis remains a critical technical challenge due to the very low concentration of ctDNA in peripheral blood samples, particularly in cancer patients following a curative-intent surgery or treatment. The present review summarizes the current key technical approaches that can be used to analyze ctDNA in the surveillance of MRD in solid tumors and provides a brief update on current commercial assays or platforms available for ctDNA-based MRD detection. The available evidence to date supporting ctDNA as a biomarker for detection of MRD in various types of solid tumors is also reviewed. In addition, technical and biological variables and considerations in pre-analytical and analytical steps associated with ctDNA-based MRD detection are discussed.