Signed in Blood: Circulating Tumor DNA in Cancer Diagnosis, Treatment and Screening

Abstract

With the addition of molecular testing to the oncologist’s diagnostic toolbox, patients have benefitted from the successes of gene- and immune-directed therapies. These therapies are often most effective when administered to the subset of malignancies harboring the target identified by molecular testing. An important advance in the application of molecular testing is the liquid biopsy, wherein circulating tumor DNA (ctDNA) is analyzed for point mutations, copy number alterations, and amplifications by polymerase chain reaction (PCR) and/or next-generation sequencing (NGS). The advantages of evaluating ctDNA over tissue DNA include (i) ctDNA requires only a tube of blood, rather than an invasive biopsy, (ii) ctDNA can plausibly reflect DNA shedding from multiple metastatic sites while tissue DNA reflects only the piece of tissue biopsied, and (iii) dynamic changes in ctDNA during therapy can be easily followed with repeat blood draws. Tissue biopsies allow comprehensive assessment of DNA, RNA, and protein expression in the tumor and its microenvironment as well as functional assays; however, tumor tissue acquisition is costly with a risk of complications. Herein, we review the ways in which ctDNA assessment can be leveraged to understand the dynamic changes of molecular landscape in cancers.

Blood, Toil, and Taxoteres: Biological Determinants of Treatment-Induced ctDNA Dynamics for Interpreting Tumor Response

“…Circulating tumor DNA (ctDNA) is extracellular DNA in plasma that originates from tumor cells and has emerged as a useful biomarker in non-invasive liquid biopsy ( 1 - 3 ). ctDNA abundance shows broad correlation with tumor burden and generally reflects the tumor DNA content such that clinical assays are commercially available for detection of molecular/minimal residual disease (MRD) and tumor mutational profiling ( 4 – 6 ). However, there are currently no ctDNA-based assays approved for serial monitoring during treatment to assess immediate tumor response and treatment efficacy.…”

Immunotherapy in Breast Cancer and the Potential Role of Liquid Biopsy

“…Predictive and prognostic biomarkers in oncology have played an important role in guiding treatment to improve patient outcomes ( 1 , 2 ). The recent emergence of liquid biopsy-based biomarkers from blood—e.g., circulating tumor cells (CTCs) ( 3 – 5 ) and circulating tumor DNA (ctDNA) ( 6 – 10 )—has offered minimally invasive approaches to assess tumor response and survival in early-stage and metastatic breast cancer ( 11 , 12 ). Blood-based biomarkers have addressed the limitations poised by tissue-based biomarkers because they are more readily accessible than tissue ( 13 ).…”

Liquid Biopsy as a Prognostic and Theranostic Tool for the Management of Pancreatic Ductal Adenocarcinoma

“…ctDNA has also been used in assisting in the detection and recurrence surveillance for colorectal and breast cancers. Utilizing ctDNA monitoring in these cancer types has been extremely promising in highlighting appropriate patients for particular treatment pathways and identify specific therapeutic regimes that will have the most clinical benefit (103,104).…”