{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:41:46Z","timestamp":1773787306479,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":310,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004853","name":"Chinese University of Hong Kong","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004853","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Case Reports in Oncological Medicine"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      <jats:italic>BRAFV600E<\/jats:italic>\n                      \u2010mutated metastatic colorectal cancers (mCRCs) are associated with poorer prognosis. We present a case, in which noninvasive therapeutic monitoring was performed on a patient with\n                      <jats:italic>BRAF<\/jats:italic>\n                      \u2010mutant mCRC, aiming to track disease progression and elucidate the mechanisms of response and resistance towards anti\u2010\n                      <jats:italic>BRAF<\/jats:italic>\n                      therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A 40\u2010year\u2010old man diagnosed with metastatic\n                      <jats:italic>BRAFV600E<\/jats:italic>\n                      mutant sigmoid adenocarcinoma received multiple lines of treatment, including first\u2010line chemotherapy + bevacizumab and targeted therapy of cetuximab, encorafenib \u00b1 binimetinib. Noninvasive therapeutic monitoring was performed on ctDNA using our in\u2010house designed droplet digital PCR assay and fragmentomics. We also performed serial and paired analyses of tissue, liquid biopsy, and in vitro studies at different multiple timepoints.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ctDNA and fragmentomics biomarkers were concordant with, and even preceded traditional serological and radiological biomarkers in predicting disease progression. Molecular analyses and drug testing also revealed mutations that are either potentially targetable or account for resistance, which guided the subsequent treatment regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This case demonstrates the potential application of ctDNA and fragmentomics biomarkers, molecular analyses, and drug testing in noninvasive therapeutic monitoring of\n                      <jats:italic>BRAFV600E<\/jats:italic>\n                      mutant mCRC. These illustrate the potential application of such noninvasive therapeutic monitoring in larger scale cohorts of patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/crom\/8140524","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:33:58Z","timestamp":1762508038000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Noninvasive Therapeutic Monitoring of Circulating Tumor DNA in BRAF\u2010Mutant Metastatic Colon Cancer Using Droplet Digital PCR, Next\u2010Generation Sequencing, and Fragmentomics"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1449-2953","authenticated-orcid":false,"given":"Rachel C. T.","family":"Lam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8989-1293","authenticated-orcid":false,"given":"Connie W. C.","family":"Hui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene O. L.","family":"Tse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7737-9643","authenticated-orcid":false,"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2364-8331","authenticated-orcid":false,"given":"Chit","family":"Chow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4651-677X","authenticated-orcid":false,"given":"Wei","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-1691","authenticated-orcid":false,"given":"K. C. Allen","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4802-1102","authenticated-orcid":false,"given":"Brigette B. Y.","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-5609","authenticated-orcid":false,"given":"W. K. 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