{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:24:32Z","timestamp":1793053472029,"version":"4.5.0"},"reference-count":89,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T00:00:00Z","timestamp":1626566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA023100"],"award-info":[{"award-number":["P30 CA023100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>With the addition of molecular testing to the oncologist\u2019s 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.<\/jats:p>","DOI":"10.3390\/cancers13143600","type":"journal-article","created":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T21:16:48Z","timestamp":1626643008000},"page":"3600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Signed in Blood: Circulating Tumor DNA in Cancer Diagnosis, Treatment and Screening"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4272-312X","authenticated-orcid":false,"given":"Jacob J.","family":"Adashek","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of South Florida, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Janku","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-1214","authenticated-orcid":false,"given":"Razelle","family":"Kurzrock","sequence":"additional","affiliation":[{"name":"WIN Consortium, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1001\/jama.2017.12131","article-title":"Cancer DNA in the Circulation: The Liquid Biopsy","volume":"318","author":"Husain","year":"2017","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/S1470-2045(20)30444-7","article-title":"Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): A multicentre, multicohort, phase 2a, platform trial","volume":"21","author":"Turner","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5729","DOI":"10.1158\/1078-0432.CCR-17-1439","article-title":"Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor-Based Immunotherapy","volume":"23","author":"Khagi","year":"2017","journal-title":"Clin. 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