{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:19:07Z","timestamp":1779135547287,"version":"3.51.4"},"reference-count":47,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>The EXOsome and cell-free microRNAs (miRNAs) of anti\u2013epidermal growth factor receptor (EGFR) Resistance (EXONERATE) study previously developed and validated a liquid biopsy to predict the efficacy of first-line anti-EGFR therapy in metastatic colorectal cancer (mCRC) from treatment-na\u00efve blood samples. This study evaluates the performance of the EXONERATE assay during therapy as a tool for monitoring the emergence of anti-EGFR resistance before it becomes clinically or radiologically apparent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Retrospective, single-center, longitudinal, REMARK-compliant biomarker study assessing the ability of a liquid biopsy to predict response to anti-EGFR monoclonal antibodies and to track resistance development longitudinally. Fifty-two patients with RAS wild-type mCRC provided 142 plasma samples during administration of first-line anti-EGFR\u2013based therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Baseline EXONERATE scores predicted response with 83.3% specificity and 77.3% sensitivity (area under the receiver operating characteristic curve [AUROC] = 89.4%). Longitudinal analyses demonstrated that biomarker changes closely tracked tumor burden and anticipated clinical and radiological progression, outperforming conventional tumor markers CEA and CA19-9. Stepwise optimization produced a reduced panel (four cell-free-miRNAs and five exo-miRNAs), EXONERATE-Tracking Response and Clinical Evolution (TRaCE), which retained high predictive accuracy (AUROC = 94.4%) while enabling more practical, repeated monitoring. EXONERATE-TRaCE values increased during the 3 months preceding the first clinical or radiological evidence of progression and reliably detected early progression in both left- and right-sided tumors, including patients with lung metastases, and identified resistance up to 3 months before radiological confirmation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>EXONERATE-TRaCE extends the predictive utility of the original EXONERATE assay into a practical monitoring tool. This liquid biopsy detects emerging anti-EGFR resistance earlier than conventional markers and may inform treatment monitoring and support timely clinical decision making in mCRC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-01229","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T19:59:14Z","timestamp":1779134354000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["EXONERATE-TRaCE: A Liquid Biopsy for Tracking Response to Anti\u2013Epidermal Growth Factor Receptor\u2013Based Therapy in Metastatic Colorectal Cancer"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5903-5718","authenticated-orcid":true,"given":"Toshiaki","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, 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