Faculty Collaboration Database

Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA. J Immunother Cancer 2023 Jun;11(6)

Date

06/23/2023

Pubmed ID

37349125

Pubmed Central ID

PMC10314661

DOI

10.1136/jitc-2022-006284

Scopus ID

2-s2.0-85162842966 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

Liquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be used to identify actionable mutations to personalize systemic therapy, detect post-treatment minimal residual disease (MRD), and predict responses to immunotherapy. ctDNA can also be isolated from a range of different biofluids, with the possibility of detecting locoregional MRD with increased sensitivity if sampling more proximally than blood plasma. However, ctDNA detection remains challenging in early-stage and post-treatment MRD settings where ctDNA levels are minuscule giving a high risk for false negative results, which is balanced with the risk of false positive results from clonal hematopoiesis. To address these challenges, researchers have developed ever-more elegant approaches to lower the limit of detection (LOD) of ctDNA assays toward the part-per-million range and boost assay sensitivity and specificity by reducing sources of low-level technical and biological noise, and by harnessing specific genomic and epigenomic features of ctDNA. In this review, we highlight a range of modern assays for ctDNA analysis, including advancements made to improve the signal-to-noise ratio. We further highlight the challenge of detecting ultra-rare tumor-associated variants, overcoming which will improve the sensitivity of post-treatment MRD detection and open a new frontier of personalized adjuvant treatment decision-making.

Author List

Semenkovich NP, Szymanski JJ, Earland N, Chauhan PS, Pellini B, Chaudhuri AA

Author

Nicholas Semenkovich MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Circulating Tumor DNA
Genomics
Humans
Neoplasm, Residual