{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:59:07Z","timestamp":1792180747136,"version":"4.4.0"},"reference-count":118,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The American Cancer Society estimates that over 152,000 new cases of colorectal cancer (CRC) were diagnosed in 2024, with more than 105,000 cases affecting the colon and 46,000 involving the rectum. CRC remains the second leading cause of cancer-related deaths in the United States, with an estimated 53,010 deaths in 2024. In the era of precision medicine, which incorporates molecular and environmental information into clinical decision-making, identifying patients harboring a deficiency in Deoxyribonucleic acid (DNA) repair allowed for targeted immunotherapies and significantly reduced CRC-related mortality. A significant advancement in this domain is the application of liquid biopsy, which has emerged as a promising tool for prognostication, guiding therapy, and monitoring treatment response in CRC. This review aims to comprehensively explore the role of liquid biopsy in colorectal malignancies, describing its practical applications, prognostic significance, and potential to revolutionize CRC management in the future. At the end, we also aim to show a schematic representation of showing integration of Circulating Tumor (Ct) DNA in routine clinical management of CRC. The highlight of this article is the structured and evidence-based schematic framework and its integration into future practice. The schematic pathway is designed to optimize ctDNA utilization across various stages of colorectal cancer management.<\/jats:p>","DOI":"10.3390\/cancers17152520","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:00:41Z","timestamp":1753884041000},"page":"2520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Integrating Circulating Tumor DNA into Clinical Management of Colorectal Cancer: Practical Implications and Therapeutic Challenges"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7238-1058","authenticated-orcid":false,"given":"Nikhil","family":"Vojjala","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Trinity Health Oakland Hospital, Pontiac, MI 48341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3373-736X","authenticated-orcid":false,"given":"Viktoriya","family":"Gibatova","sequence":"additional","affiliation":[{"name":"School of Medicine, Ross University, Miami, FL 33130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4129-2057","authenticated-orcid":false,"given":"Raj N.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kansas University School of Medicine-Wichita, Wichita, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakshi","family":"Singal","sequence":"additional","affiliation":[{"name":"Department of Oncology, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9196-8425","authenticated-orcid":false,"given":"Rishab","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Trinity Health Oakland Hospital, Pontiac, MI 48341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-2253","authenticated-orcid":false,"given":"Geetha","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Trinity Health Oakland Hospital, Pontiac, MI 48341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Riggins","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1582-6320","authenticated-orcid":false,"given":"Nagaishwarya","family":"Moka","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, Lincoln Memorial University, Harrogate, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Saad El, D.K., Loree, J.M., Sayre, E.C., Gill, S., Brown, C.J., Dau, H., and Vera De, M.A. (2020). Trends in the epidemiology of young-onset colorectal cancer: A worldwide systematic review. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-06766-9"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/COC.0b013e3181fe41ed","article-title":"Trends in colorectal cancer incidence by anatomic site and disease stage in the United States from 1976 to 2005","volume":"34","author":"Cheng","year":"2011","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1056\/NEJMoa071834","article-title":"Cetuximab for the treatment of colorectal cancer","volume":"357","author":"Jonker","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1200\/JCO.2006.08.1620","article-title":"Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer","volume":"25","author":"Peeters","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Su, D.W., and Nieva, J. (2017). Biophysical technologies for understanding circulating tumor cell biology and metastasis. Transl. Lung Cancer Res., 6.","DOI":"10.21037\/tlcr.2017.05.08"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nassar, F.J., Msheik, Z.S., Nasr, R.R., and Temraz, S.N. (2021). Methylated circulating tumor DNA as a biomarker for colorectal cancer diagnosis, prognosis, and prediction. Clin. Epigenet., 13.","DOI":"10.1186\/s13148-021-01095-5"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.gpb.2016.12.004","article-title":"Circulating Tumor DNA as Biomarkers for Cancer Detection","volume":"15","author":"Han","year":"2017","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1056\/NEJMoa0800668","article-title":"Detection of mutations in EGFR in circulating lung-cancer cells","volume":"359","author":"Maheswaran","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1002\/cncr.24997","article-title":"Plasma cell-free DNA in ovarian cancer: An independent prognostic biomarker","volume":"116","author":"Kamat","year":"2010","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lianidou, E.S., Mavroudis, D., Sotiropoulou, G., Agelaki, S., and Pantel, K. (2010). What\u2019s new on circulating tumor cells? A meeting report. Breast Cancer Res., 12.","DOI":"10.1186\/bcr2601"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.molmed.2010.07.001","article-title":"Circulating tumour cells in cancer patients: Challenges and perspectives","volume":"16","author":"Pantel","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrc3066","article-title":"Cell-free nucleic acids as biomarkers in cancer patients","volume":"11","author":"Schwarzenbach","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Arechederra, M., \u00c1vila, M.A., and Berasain, C. (2020). Liquid biopsy for cancer management: A revolutionary but still limited new tool for precision medicine. Adv. Lab. Med., 1.","DOI":"10.1515\/almed-2020-0009"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Warren, J.D., Xiong, W., Bunker, A.M., Vaughn, C.P., Furtado, L.V., Roberts, W.L., Fang, J.C., Samowitz, W.S., and Heichman, K.A. (2011). Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer. BMC Med., 9.","DOI":"10.1186\/1741-7015-9-133"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S1470-2045(08)70340-1","article-title":"Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: A reanalysis of IMMC38 trial data","volume":"10","author":"Scher","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1200\/JCO.2010.28.7045","article-title":"Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer","volume":"29","author":"Krebs","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10555-012-9398-0","article-title":"Clinical application of circulating tumor cells in breast cancer: Overview of the current interventional trials","volume":"32","author":"Bidard","year":"2013","journal-title":"Cancer Metastasis Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6248","DOI":"10.1158\/1078-0432.CCR-18-1128","article-title":"Analysis of Circulating Tumor DNA and Clinical Correlates in Patients with Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma","volume":"24","author":"Kato","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1158\/1535-7163.MCT-17-1038","article-title":"Next-Generation Sequencing of Tissue and Circulating Tumor DNA: The UC San Diego Moores Center for Personalized Cancer Therapy Experience with Breast Malignancies","volume":"18","author":"Shatsky","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1007\/s00432-011-1000-6","article-title":"Efficacy control of therapy using circulating epithelial tumor cells (CETC) as \u201cliquid biopsy\u201d: Trastuzumab in HER2\/neu-positive breast carcinoma","volume":"137","author":"Pachmann","year":"2011","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4589","DOI":"10.1073\/pnas.95.8.4589","article-title":"Detection and characterization of carcinoma cells in the blood","volume":"95","author":"Racila","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41571-019-0187-3","article-title":"Liquid biopsy and minimal residual disease\u2014Latest advances and implications for cure","volume":"16","author":"Pantel","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41571-018-0035-x","article-title":"Clinical utility of circulating non-coding RNAs\u2014An update","volume":"15","author":"Anfossi","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kalluri, R., and LeBleu, V.S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367.","DOI":"10.1126\/science.aau6977"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ccell.2017.07.004","article-title":"Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets","volume":"32","author":"Best","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gahlawat, A.W., Witte, T., Sinn, P., and Schott, S. (2023). Circulating cf-miRNA as a more appropriate surrogate liquid biopsy marker than cfDNA for ovarian cancer. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-32243-x"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, S., Lin, Y., Zhang, Y., Qiu, X., Pan, Y., Yeung, S.-C.J., and Zhang, H. (2022). Complex RNA world in small extracellular vesicles for liquid biopsy in cancer management. Extracell. Vesicle, 1.","DOI":"10.1016\/j.vesic.2022.100015"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.ccell.2015.10.007","article-title":"Tumor-Educated Platelets as Liquid Biopsy in Cancer Patients","volume":"28","author":"Joosse","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Dell\u2019Olio, F., Su, J., Huser, T., Sottile, V., Cort\u00e9s-Hern\u00e1ndez, L.E., and Alix-Panabi\u00e8res, C. (2021). Photonic technologies for liquid biopsies: Recent advances and open research challenges. Laser Photonics Rev., 15.","DOI":"10.1002\/lpor.202000255"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.csbj.2018.05.002","article-title":"ctDNA and CTCs in Liquid Biopsy\u2014Current Status and Where We Need to Progress","volume":"16","author":"Neumann","year":"2018","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41576-018-0071-5","article-title":"Current and future perspectives of liquid biopsies in genomics-driven oncology","volume":"20","author":"Heitzer","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Santonja, A., Cooper, W.N., Eldridge, M.D., Edwards, P.A., Morris, J.A., Edwards, A.R., Zhao, H., Heider, K., Couturier, D.L., and Vijayaraghavan, A. (2023). Comparison of tumor-informed and tumor-na\u00efve sequencing assays for ctDNA detection in breast cancer. EMBO Mol. Med., 15.","DOI":"10.15252\/emmm.202216505"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chan, H.T., Nagayama, S., Otaki, M., Chin, Y.M., Fukunaga, Y., Ueno, M., Nakamura, Y., and Low, S.K. (2023). Tumor-informed or tumor-agnostic circulating tumor DNA as a biomarker for risk of recurrence in resected colorectal cancer patients. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1055968"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Luo, H., Zhao, Q., Wei, W., Zheng, L., Yi, S., Li, G., Wang, W., Sheng, H., Pu, H., and Mo, H. (2020). Circulating tumor DNA methylation profiles enable early diagnosis, prognosis prediction, and screening for colorectal cancer. Sci. Transl. Med., 12.","DOI":"10.1126\/scitranslmed.aax7533"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.annonc.2020.02.011","article-title":"Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA","volume":"31","author":"Liu","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/j.annonc.2020.06.008","article-title":"Response to W.C. Taylor, and C. Fiala and E.P. Diamandis","volume":"31","author":"Liu","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1093\/clinchem\/hvaa258","article-title":"Cell-Free DNA Fragmentomics: The New \u201cOmics\u201d on the Block","volume":"66","author":"Chiu","year":"2020","journal-title":"Clin. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nrclinonc.2013.110","article-title":"Liquid biopsy: Monitoring cancer-genetics in the blood","volume":"10","author":"Crowley","year":"2013","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3888","DOI":"10.21037\/tlcr-21-564","article-title":"A large-scale, multicentered trial evaluating the sensitivity and specificity of digital PCR versus ARMS-PCR for detecting ctDNA-based EGFR p.T790M in non-small-cell lung cancer patients","volume":"10","author":"Xu","year":"2021","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_41","first-page":"158","article-title":"Diagnostic Accuracy of Next Generation Sequencing Panel using Circulating Tumor DNA in Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis","volume":"7","author":"Ho","year":"2020","journal-title":"J. Health Econ. Outcomes Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s40291-024-00725-x","article-title":"Clinical Validity and Utility of Circulating Tumor DNA (ctDNA) Testing in Advanced Non-small Cell Lung Cancer (aNSCLC): A Systematic Literature Review and Meta-analysis","volume":"28","author":"Chen","year":"2024","journal-title":"Mol. Diagn. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1158\/2159-8290.CD-20-1311","article-title":"Liquid Biopsy: From Discovery to Clinical Application","volume":"11","author":"Pantel","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Malkawi, W., Lutfi, A., Afghan, M.K., Shah, L.M., Costandy, L., Ramirez, A.B., George, T.C., Toor, F., Salem, A.K., and Kasi, P.M. (2023). Circulating tumour cell enumeration, biomarker analyses, and kinetics in patients with colorectal cancer and other GI malignancies. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1305181"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Molparia, B., Oliveira, G., Wagner, J.L., Spencer, E.G., and Torkamani, A. (2018). A feasibility study of colorectal cancer diagnosis via circulating tumor DNA derived CNV detection. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196826"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1373\/clinchem.2014.222679","article-title":"Circulating tumor DNA as a liquid biopsy for cancer","volume":"61","author":"Heitzer","year":"2015","journal-title":"Clin. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Buscail, E., Alix-Panabi\u00e8res, C., Quincy, P., Cauvin, T., Chauvet, A., Degrandi, O., Camount, C., Verdon, S., Lamrissi, I., and Moranviller, I. (2019). High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery. Cancers, 11.","DOI":"10.3390\/cancers11111656"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Buscail, E., Maulat, C., Muscari, F., Chiche, L., Cordelier, P., Dabernat, S., Panabieres, C.A., and Buscail, L. (2019). Liquid Biopsy Approach for Pancreatic Ductal Adenocarcinoma. Cancers, 11.","DOI":"10.3390\/cancers11060852"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tie, J., Wang, Y., Tomasetti, C., Li, L., Springer, S., Kinde, I., Silliman, N., Tacey, M., Wong, H.L., and Christie, M. (2016). Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci. Transl. Med., 8.","DOI":"10.1126\/scitranslmed.aaf6219"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bettegowda, C., Sausen, M., Leary, R.J., Kinde, I., Wang, Y., Agrawal, N., Barlett, B.R., Wang, H., Luber, B., and Alani, R.M. (2014). Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med., 6.","DOI":"10.1093\/neuonc\/nou206.24"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature11219","article-title":"The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers","volume":"486","author":"Diaz","year":"2012","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Liu, W., Li, Y., Tang, Y., Song, Q., Wang, J., Li, N., Chen, S., Shi, J., Wang, S., and Li, Y. (2022). Response prediction and risk stratification of patients with rectal cancer after neoadjuvant therapy through an analysis of circulating tumour DNA. EBioMedicine, 78.","DOI":"10.1016\/j.ebiom.2022.103945"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1158\/1078-0432.CCR-23-3660","article-title":"Minimal residual disease using a plasma-only circulating tumor DNA assay to predict recurrence of metastatic colorectal cancer following curative intent treatment","volume":"30","author":"Parikh","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1158\/1078-0432.CCR-24-0226","article-title":"Tissue-free liquid biopsies combining genomic and methylation signals for minimal residual disease detection in patients with early colorectal cancer from the UK TRACC part B study","volume":"30","author":"Slater","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Min, L., Chen, J., Yu, M., and Liu, D. (2023). Using circulating tumor DNA as a novel biomarker to screen and diagnose colorectal cancer: A meta-analysis. J. Clin. Med., 12.","DOI":"10.3390\/jcm12020408"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1038\/s41591-024-03254-6","article-title":"ctDNA-based molecular residual disease and survival in resectable colorectal cancer","volume":"30","author":"Nakamura","year":"2024","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.annonc.2023.11.009","article-title":"Unraveling the potential clinical utility of circulating tumor DNA detection in colorectal cancer\u2014Evaluation in a nationwide Danish cohort","volume":"35","author":"Henriksen","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1111\/codi.17039","article-title":"ctDNA as a predictor of outcome after curative resection for locally advanced rectal cancer: Systematic review and meta-analysis","volume":"26","author":"Nassar","year":"2024","journal-title":"Color. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1001\/jamaoncol.2019.0528","article-title":"Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients with Stages I to III Colorectal Cancer","volume":"5","author":"Reinert","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1093\/annonc\/mdz390","article-title":"Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer","volume":"30","author":"Tarazona","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1001\/jamaoncol.2019.3616","article-title":"Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer","volume":"5","author":"Tie","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1002\/ijc.33312","article-title":"Prognostic significance of postsurgery circulating tumor DNA in nonmetastatic colorectal cancer: Individual patient pooled analysis of three cohort studies","volume":"148","author":"Tie","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1158\/1078-0432.CCR-20-2299","article-title":"Serial Circulating Tumor DNA in Predicting and Monitoring the Effect of Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer: A Prospective Multicenter Study","volume":"27","author":"Zhou","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1158\/1078-0432.CCR-21-2404","article-title":"Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences","volume":"28","author":"Henriksen","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5638","DOI":"10.1158\/1078-0432.CCR-21-0271","article-title":"Prognostic Value and Relation with Adjuvant Treatment Duration of ctDNA in Stage III Colon Cancer: A Post Hoc Analysis of the PRODIGE-GERCOR IDEA-France Trial","volume":"27","author":"Taieb","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5586","DOI":"10.1158\/1078-0432.CCR-21-0410","article-title":"Minimal Residual Disease Detection using a Plasma-only Circulating Tumor DNA Assay in Patients with Colorectal Cancer","volume":"27","author":"Parikh","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ejca.2022.04.010","article-title":"Postoperative circulating tumor DNA combined with consensus molecular subtypes can better predict outcomes in stage III colon cancers: A prospective cohort study","volume":"169","author":"Li","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1056\/NEJMoa2200075","article-title":"Circulating tumor DNA analyses as markers of recurrence risk and adjuvant benefit in stage II colon cancer","volume":"386","author":"Tie","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41591-022-02115-4","article-title":"Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer","volume":"29","author":"Kotani","year":"2023","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"S1268","DOI":"10.1016\/j.annonc.2023.10.020","article-title":"LBA28 The PEGASUS trial: Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients","volume":"34","author":"Lonardi","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1097\/SLA.0000000000005856","article-title":"Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients with Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery","volume":"278","author":"Dhiman","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Lygre, K.B., Forthun, R.B., H\u00f8ys\u00e6ter, T., Hjelle, S.M., Eide, G.E., Gjertsen, B.T., Pfeffer, F., and Hovland, R. (2024). Assessment of postoperative circulating tumour DNA to predict early recurrence in patients with stage I-III right-sided colon cancer: Prospective observational study. BJS Open, 8.","DOI":"10.1093\/bjsopen\/zrad146"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Morris, V.K., Yothers, G., Kopetz, S., Puhalla, S.L., Lucas, P.C., Iqbal, A., Boland, P.M., Deming, D.A., Scott, A.J., and Lim, H.J. (2024). Phase II results of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA) phase II\/III study. J. Clin. Oncol., 42.","DOI":"10.1200\/JCO.2024.42.3_suppl.5"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kasi, P.M., Aushev, V.N., Ensor, J., Langer, N., Wang, C.G., Cannon, T.L., Berim, L.D., Feinstein, T., Grothey, A., and McCollom, J.W. (2024). Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II\/III colorectal cancer (CRC): Interim analysis of BESPOKE CRC study. J. Clin. Oncol., 42.","DOI":"10.1200\/JCO.2024.42.3_suppl.9"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Yukami, H., Nakamura, Y., Mishima, S., Ando, K., Bando, H., Watanabe, J., Hirata, K., Akazawa, N., Ikeda, M., and Yokota, M. (2024). Circulating tumor DNA (ctDNA) dynamics in patients with colorectal cancer (CRC) with molecular residual disease: Updated analysis from GALAXY study in the CIRCULATE-JAPAN. J. Clin. Oncol., 42.","DOI":"10.1200\/JCO.2024.42.3_suppl.6"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ejca.2020.11.025","article-title":"Circulating tumour DNA as a biomarker in resectable and irresectable stage IV colorectal cancer; a systematic review and meta-analysis","volume":"144","author":"Jones","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/s41416-022-01816-4","article-title":"Circulating tumour DNA and its clinical utility in predicting treatment response or survival in patients with metastatic colorectal cancer: A systematic review and meta-analysis","volume":"127","author":"Callesen","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/s41416-022-02017-9","article-title":"The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: A systematic review and meta-analysis","volume":"128","author":"Faulkner","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Do, Q., Katiyar, V., Malloy, M., and Sharma, V.R. (2023). Circulating tumor DNA detection as a prognostic tool in patients with localized colon cancer: A systematic review and meta-analysis. J. Clin. Oncol., 41.","DOI":"10.1200\/JCO.2023.41.16_suppl.e15629"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e1198","DOI":"10.1093\/oncolo\/oyad151","article-title":"Prognostic Value of ctDNA Detection in Patients with Locally Advanced Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Systematic Review and Meta-analysis","volume":"28","author":"Chang","year":"2023","journal-title":"Oncologist"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1111\/cas.15707","article-title":"Single-cell next-generation sequencing of circulating tumor cells in patients with neuroblastoma","volume":"114","author":"Kojima","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Nagasawa, S., Kashima, Y., Suzuki, A., and Suzuki, Y. (2021). Single-cell and spatial analyses of cancer cells: Toward elucidating the molecular mechanisms of clonal evolution and drug resistance acquisition. Inflamm. Regen., 41.","DOI":"10.1186\/s41232-021-00170-x"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Sherwood, J.L., Corcoran, C., Brown, H., Sharpe, A.D., Musilova, M., and Kohlmann, A. (2016). Optimised pre-analytical methods improve KRAS mutation detection in circulating tumour DNA (ctDNA) from patients with non-small cell lung cancer (NSCLC). PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150197"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Medina Diaz, I., Nocon, A., Mehnert, D.H., Fredebohm, J., Diehl, F., and Holtrup, F. (2016). Performance of Streck cfDNA blood collection tubes for liquid biopsy testing. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166354"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/nm.1789","article-title":"Circulating mutant DNA to assess tumor dynamics","volume":"14","author":"Diehl","year":"2008","journal-title":"Nat. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Toth, K., Sipos, F., Kalmar, A., Patai, A.V., Wichmann, B., Stoehr, R., Golcher, H., Scheller, V., Tulassay, Z., and Molnar, B. (2012). Detection of methylated SEPT9 in plasma is a reliable screening method for both left-and right-sided colon cancers. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046000"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Nguyen, T.H.H., Vu, G.H., Nguyen, T.T., Nguyen, T.A., Tran, V.U., Vu, L.T., Huong Nguyen, G.T., Duy Nguyen, N., Tran, T.H., and Chi Nguyen, V.T. (2025). Combination of Hotspot Mutations with Methylation and Fragmentomic Profiles to Enhance Multi-Cancer Early Detection. Cancer Med., 14.","DOI":"10.1002\/cam4.70575"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1093\/annonc\/mdu239","article-title":"Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: A proof-of-principle","volume":"25","author":"Weigelt","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor heterogeneity and branched evolution revealed by multiregion sequencing","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.pharmthera.2017.02.003","article-title":"Capturing tumor heterogeneity and clonal evolution in solid cancers using circulating tumor DNA analysis","volume":"174","author":"Perdigones","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s41416-023-02300-3","article-title":"Personalised circulating tumour DNA assay with large-scale mutation coverage for sensitive minimal residual disease detection in colorectal cancer","volume":"129","author":"Ryoo","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/clinchem\/hvad188","article-title":"A practical approach to interpreting circulating tumor DNA in the management of gastrointestinal cancers","volume":"70","author":"Allan","year":"2024","journal-title":"Clin. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.5858\/arpa.2018-0901-SA","article-title":"Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review","volume":"142","author":"Merker","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Linder, M.W., Huggett, J.F., Baluchova, K., Capoluongo, E.D., Payne, D.A., Salinas, A.V., Haselmann, V., Ashavaid, T., Pan, S., and Ahmad-Nejad, P. (2023). Results from an IFCC global survey on laboratory practices for the analysis of circulating tumor DNA. Clin. Chim. Acta, 547.","DOI":"10.1016\/j.cca.2023.117398"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1200\/JCO.21.02615","article-title":"Using Circulating Tumor DNA in Colorectal Cancer: Current and Evolving Practices","volume":"40","author":"Malla","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1080\/0284186X.2020.1806357","article-title":"Circulating tumor DNA as a marker of minimal residual disease following local treatment of metastases from colorectal cancer","volume":"59","author":"Boysen","year":"2020","journal-title":"Acta Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1002\/ijc.10526","article-title":"Detection of free-circulating tumor-associated DNA in plasma of colorectal cancer patients and its association with prognosis","volume":"100","author":"Lecomte","year":"2002","journal-title":"Int. J. Cancer."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Van Cutsem, E., Verheul, H.M., Flamen, P., Rougier, P., Beets-Tan, R., Glynne-Jones, R., and Seufferlein, T. (2016). Imaging in colorectal cancer: Progress and challenges for the clinicians. Cancers, 8.","DOI":"10.3390\/cancers8090081"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5437","DOI":"10.1158\/1078-0432.CCR-17-0510","article-title":"Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer","volume":"23","author":"Reinert","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1056\/NEJMoa2200075","article-title":"Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer","volume":"386","author":"Tie","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1136\/gutjnl-2017-314178","article-title":"Functional imaging and circulating biomarkers of response to regorafenib in treatment-refractory metastatic colorectal cancer patients in a prospective phase II study","volume":"67","author":"Khan","year":"2018","journal-title":"Gut"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Pappas, L., Yaeger, R., Kasi, P.M., Shah, M.A., Azad, N.S., Horick, N.K., Corcoran, R.B., Diaz, L.A., and Parikh, A.R. (2024). Early identification and treatment of occult metastatic disease in stage III colon cancer (SU2C ACT3 clinical trial). Am. Soc. Clin. Oncol., 42.","DOI":"10.1200\/JCO.2024.42.3_suppl.148"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1200\/JCO.24.00648","article-title":"Combined Analyses of Circulating Tumor DNA and Immunoscore in Patients with Stage III Colon Cancer: A Post Hoc Analysis of the PRODIGE-GERCOR IDEA-France\/HORG-IDEA-Greece Trials","volume":"43","author":"Taieb","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"S354","DOI":"10.4103\/jcrt.jcrt_1072_22","article-title":"Analysis of SDC2 gene promoter methylation in whole blood for noninvasive early detection of colorectal cancer","volume":"18","author":"Siri","year":"2022","journal-title":"J. Cancer Res. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Sidaway, P. (2020). Diagnosis using methylation. Nat. Rev. Clin. Oncol., 17.","DOI":"10.1038\/s41571-020-0334-x"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Shweikeh, F., Zeng, Y., Jabir, A.R., Whittenberger, E., Kadatane, S.P., Huang, Y., Mouchli, M., and Castillo, D.R. (2024). The emerging role of blood-based biomarkers in early detection of colorectal cancer: A systematic review. Cancer Treat. Res. Commun., 42.","DOI":"10.1016\/j.ctarc.2025.100872"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/DLMT1294","article-title":"Multi-cancer early detection tests for general population screening: A systematic literature review","volume":"29","author":"Wade","year":"2025","journal-title":"Health Technol. Assess."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Schraa, S., Van Rooijen, K., Van Der Kruijssen, D., Rubio Alarc\u00f3n, C., Phallen, J., Sausen, M., Simmons, J., Coupe, V.M.H., Van Grevenstein, W.M.U., and Elias, S. (2020). Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): Study protocol for a trial within a cohort study. BMC Cancer, 20.","DOI":"10.1016\/j.annonc.2020.08.631"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1111\/cas.14926","article-title":"CIRCULATE-Japan: Circulating tumor DNA\u2013guided adaptive platform trials to refine adjuvant therapy for colorectal cancer","volume":"112","author":"Taniguchi","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Hashimoto, T., Tsukada, Y., Ito, M., Kanato, K., Mizusawa, J., Fukuda, H., Tsukamoto, S., Takashima, A., and Kanemitsu, Y. (2023). Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: Study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study). BMJ Open, 13.","DOI":"10.1136\/bmjopen-2023-073217"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1136\/gutjnl-2024-331956","article-title":"Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments","volume":"73","author":"Campani","year":"2024","journal-title":"Gut"},{"key":"ref_112","first-page":"53","article-title":"Molecular Residual Disease-guided Adjuvant Treatment in Resected Colorectal Cancer: Focus on CIRCULATE-Japan","volume":"22","author":"Sato","year":"2023","journal-title":"Clin. Color. Cancer"},{"key":"ref_113","unstructured":"Guardant Health (2025, July 27). Guardant Reveal Product Sheet. Available online: https:\/\/www.guardantcomplete.com\/hcp\/solutions\/guardant-reveal."},{"key":"ref_114","unstructured":"Foundation Medicine (2025, July 27). FoundationOne Tracker Technical Overview. Available online: https:\/\/www.foundationmedicine.com\/test\/foundationone-liquid-cdx?utm_source=google&utm_medium=cpc&utm_campaign=liquid-cdx&utm_content=general-ub&utm_term=ctdna%20t."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"9530","DOI":"10.1073\/pnas.1105422108","article-title":"Detection and quantification of rare mutations with massively parallel sequencing","volume":"108","author":"Kinde","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/S1470-2045(15)00223-5","article-title":"Global cancer surgery: Delivering safe, affordable, and timely cancer surgery","volume":"16","author":"Sullivan","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nrclinonc.2017.14","article-title":"Integrating liquid biopsies into the management of cancer","volume":"14","author":"Siravegna","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1200\/JCO.2015.62.0096","article-title":"Cancer Genomics: Diversity and Disparity Across Ethnicity and Geography","volume":"34","author":"Tan","year":"2016","journal-title":"J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2520\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:19:12Z","timestamp":1760033952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2520"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,30]]},"references-count":118,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["cancers17152520"],"URL":"https:\/\/doi.org\/10.3390\/cancers17152520","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,30]]}}}