{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:16:18Z","timestamp":1787926578795,"version":"build-2784847793"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastrointest Canc"],"DOI":"10.1007\/s12029-026-01564-1","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:16:14Z","timestamp":1787922974000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HER2-Targeted Therapy for Metastatic Colorectal Cancer: Current Evidence, Patient Selection, and Practical Treatment Sequencing"],"prefix":"10.1007","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1994-4795","authenticated-orcid":false,"given":"Tamotsu","family":"Sagawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nagashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koshi","family":"Fujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"1564_CR1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.annonc.2022.10.003","volume":"34","author":"A Cervantes","year":"2023","unstructured":"Cervantes A, Adam R, Rosell\u00f3 S, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:10\u201332.","journal-title":"Ann Oncol"},{"key":"1564_CR2","unstructured":"National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 3.2024."},{"key":"1564_CR3","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1200\/JCO.22.01690","volume":"41","author":"VK Morris","year":"2023","unstructured":"Morris VK, Kennedy EB, Baxter NN, et al. Treatment of metastatic colorectal cancer: ASCO guideline. J Clin Oncol. 2023;41:678\u2013700.","journal-title":"J Clin Oncol"},{"key":"1564_CR4","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1001\/jama.2023.4428","volume":"329","author":"J Watanabe","year":"2023","unstructured":"Watanabe J, Muro K, Shitara K, et al. Panitumumab vs bevacizumab added to standard first-line chemotherapy and overall survival among patients with RAS wild-type, left-sided metastatic colorectal cancer: the PARADIGM randomized clinical trial. JAMA. 2023;329:1271\u201382.","journal-title":"JAMA"},{"key":"1564_CR5","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1001\/jama.2017.7105","volume":"317","author":"AP Venook","year":"2017","unstructured":"Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA. 2017;317:2392\u2013401.","journal-title":"JAMA"},{"key":"1564_CR6","doi-asserted-by":"publisher","first-page":"3046","DOI":"10.1158\/1078-0432.CCR-18-3389","volume":"25","author":"G Siravegna","year":"2019","unstructured":"Siravegna G, Sartore-Bianchi A, Nagy RJ, et al. Plasma HER2 copy number predicts response to HER2-targeted therapy in metastatic colorectal cancer. Clin Cancer Res. 2019;25:3046\u201353.","journal-title":"Clin Cancer Res"},{"key":"1564_CR7","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1038\/modpathol.2015.98","volume":"28","author":"E Valtorta","year":"2015","unstructured":"Valtorta E, Martino C, Sartore-Bianchi A, et al. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Mod Pathol. 2015;28:1481\u201391.","journal-title":"Mod Pathol"},{"key":"1564_CR8","doi-asserted-by":"publisher","first-page":"103097","DOI":"10.1016\/j.ctrv.2026.103097","volume":"144","author":"S Siena","year":"2026","unstructured":"Siena S, Chalabi M, Goodwin R, et al. Diagnosis and treatment of human epidermal growth factor receptor 2-positive metastatic colorectal cancer: a systematic literature review. Cancer Treat Rev. 2026;144:103097.","journal-title":"Cancer Treat Rev"},{"key":"1564_CR9","doi-asserted-by":"publisher","first-page":"10213","DOI":"10.1038\/s41467-024-53223-3","volume":"15","author":"S Siena","year":"2024","unstructured":"Siena S, Raghav K, Masuishi T, et al. HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01. Nat Commun. 2024;15:10213.","journal-title":"Nat Commun"},{"key":"1564_CR10","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1158\/2159-8290.CD-11-0109","volume":"1","author":"A Bertotti","year":"2011","unstructured":"Bertotti A, Migliardi G, Galimi F, et al. A molecularly annotated platform of patient-derived xenografts identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2011;1:508\u201323.","journal-title":"Cancer Discov"},{"key":"1564_CR11","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1634\/theoncologist.2018-0785","volume":"24","author":"A Sartore-Bianchi","year":"2019","unstructured":"Sartore-Bianchi A, Amatu A, Porcu L, et al. HER2 positivity predicts unresponsiveness to EGFR-targeted treatment in metastatic colorectal cancer. Oncologist. 2019;24:1395\u2013402.","journal-title":"Oncologist"},{"key":"1564_CR12","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1093\/oncolo\/oyad200","volume":"28","author":"TS Bekaii-Saab","year":"2023","unstructured":"Bekaii-Saab TS, Lach K, Hsu LI, et al. Impact of anti-EGFR therapies on HER2-positive metastatic colorectal cancer: a systematic literature review and meta-analysis of clinical outcomes. Oncologist. 2023;28:885\u201393.","journal-title":"Oncologist"},{"key":"1564_CR13","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.1093\/annonc\/mdx546","volume":"28","author":"C Cremolini","year":"2017","unstructured":"Cremolini C, Morano F, Moretto R, et al. Negative hyper-selection of metastatic colorectal cancer patients for anti-EGFR monoclonal antibodies: the PRESSING case-control study. Ann Oncol. 2017;28:3009\u201314.","journal-title":"Ann Oncol"},{"key":"1564_CR14","first-page":"e2100399","volume":"6","author":"G Randon","year":"2022","unstructured":"Randon G, Fuc\u00e0 G, Rossini D, et al. Negative ultraselection of patients with RAS\/BRAF wild-type metastatic colorectal cancer for anti-EGFR treatment. JCO Precis Oncol. 2022;6:e2100399.","journal-title":"JCO Precis Oncol"},{"key":"1564_CR15","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/S1470-2045(16)00150-9","volume":"17","author":"A Sartore-Bianchi","year":"2016","unstructured":"Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12\/13 wild-type, HER2-positive metastatic colorectal cancer: the HERACLES trial. Lancet Oncol. 2016;17:738\u201346.","journal-title":"Lancet Oncol"},{"key":"1564_CR16","first-page":"256","volume":"19","author":"F Tosi","year":"2020","unstructured":"Tosi F, Sartore-Bianchi A, Lonardi S, et al. Long-term clinical outcome of trastuzumab and lapatinib for HER2-positive metastatic colorectal cancer. Clin Colorectal Cancer. 2020;19:256\u2013e2622.","journal-title":"Clin Colorectal Cancer"},{"key":"1564_CR17","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/S1470-2045(18)30904-5","volume":"20","author":"F Meric-Bernstam","year":"2019","unstructured":"Meric-Bernstam F, Hurwitz H, Raghav KPS, et al. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: an updated report from MyPathway. Lancet Oncol. 2019;20:518\u201330.","journal-title":"Lancet Oncol"},{"key":"1564_CR18","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1038\/s41591-021-01553-w","volume":"27","author":"Y Nakamura","year":"2021","unstructured":"Nakamura Y, Okamoto W, Kato T, et al. Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: the TRIUMPH trial. Nat Med. 2021;27:1899\u2013903.","journal-title":"Nat Med"},{"key":"1564_CR19","doi-asserted-by":"publisher","first-page":"e000911","DOI":"10.1136\/esmoopen-2020-000911","volume":"5","author":"A Sartore-Bianchi","year":"2020","unstructured":"Sartore-Bianchi A, Lonardi S, Martino C, et al. Pertuzumab and trastuzumab emtansine in patients with HER2-amplified metastatic colorectal cancer: the phase II HERACLES-B trial. ESMO Open. 2020;5:e000911.","journal-title":"ESMO Open"},{"key":"1564_CR20","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/S1470-2045(23)00150-X","volume":"24","author":"JH Strickler","year":"2023","unstructured":"Strickler JH, Cercek A, Siena S, et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer: MOUNTAINEER. Lancet Oncol. 2023;24:496\u2013508.","journal-title":"Lancet Oncol"},{"key":"1564_CR21","doi-asserted-by":"publisher","first-page":"4326","DOI":"10.1158\/1078-0432.CCR-23-1041","volume":"29","author":"SJ Casak","year":"2023","unstructured":"Casak SJ, Horiba MN, McKee AE, et al. FDA approval summary: tucatinib with trastuzumab for advanced unresectable or metastatic, chemotherapy-refractory, HER2-positive RAS wild-type colorectal cancer. Clin Cancer Res. 2023;29:4326\u201331.","journal-title":"Clin Cancer Res"},{"key":"1564_CR22","doi-asserted-by":"publisher","first-page":"3332","DOI":"10.1038\/s41467-023-38032-4","volume":"14","author":"T Yoshino","year":"2023","unstructured":"Yoshino T, Di Bartolomeo M, Raghav K, et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun. 2023;14:3332.","journal-title":"Nat Commun"},{"key":"1564_CR23","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/S1470-2045(24)00380-2","volume":"25","author":"KPS Raghav","year":"2024","unstructured":"Raghav KPS, Siena S, Takashima A, et al. Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer: DESTINY-CRC02. Lancet Oncol. 2024;25:1147\u201362.","journal-title":"Lancet Oncol"},{"issue":"16suppl","key":"1564_CR24","doi-asserted-by":"publisher","first-page":"3505","DOI":"10.1200\/JCO.2026.44.16_suppl.3505","volume":"44","author":"J Li","year":"2026","unstructured":"Li J, Yuan Y, Liu TS, et al. Phase 3 trial of trastuzumab rezetecan vs standard of care (SOC) for chemotherapy-refractory, HER2-positive, advanced colorectal cancer (CRC). J Clin Oncol. 2026;44(16suppl):3505. https:\/\/doi.org\/10.1200\/JCO.2026.44.16_suppl.3505.","journal-title":"J Clin Oncol"},{"key":"1564_CR25","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.3390\/cancers18061007","volume":"18","author":"ND Kendsersky","year":"2026","unstructured":"Kendsersky ND, Erlick MR, Chen EY, Kennecke HF. The evolving role for repeat molecular testing in metastatic colorectal cancer. Cancers. 2026;18:1007.","journal-title":"Cancers"},{"key":"1564_CR26","doi-asserted-by":"publisher","first-page":"460","DOI":"10.3390\/genes17040460","volume":"17","author":"P Garcia Pastor","year":"2026","unstructured":"Garcia Pastor P, Saoudi Gonz\u00e1lez N, Salva F, et al. Genomic landscape, targeted therapies, and mechanisms of resistance in molecularly selected metastatic colorectal cancer patients. Genes. 2026;17:460.","journal-title":"Genes"},{"key":"1564_CR27","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1200\/PO.19.00154","volume":"4","author":"S Fujii","year":"2020","unstructured":"Fujii S, Magliocco AM, Kim J, et al. International harmonization of provisional diagnostic criteria for ERBB2-amplified metastatic colorectal cancer allowing for screening by next-generation sequencing panel. JCO Precis Oncol. 2020;4:6\u201319.","journal-title":"JCO Precis Oncol"},{"key":"1564_CR28","doi-asserted-by":"publisher","first-page":"3453","DOI":"10.18632\/oncotarget.6498","volume":"7","author":"N Takegawa","year":"2016","unstructured":"Takegawa N, Yonesaka K, Sakai K, et al. HER2 genomic amplification in circulating tumor DNA from patients with cetuximab-resistant colorectal cancer. Oncotarget. 2016;7:3453\u201360.","journal-title":"Oncotarget"},{"key":"1564_CR29","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1158\/2159-8290.CD-14-1211","volume":"5","author":"SM Kavuri","year":"2015","unstructured":"Kavuri SM, Jain N, Galimi F, et al. HER2 activating mutations are targets for colorectal cancer treatment. Cancer Discov. 2015;5:832\u201341.","journal-title":"Cancer Discov"},{"key":"1564_CR30","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1080\/14796694.2024.2441101","volume":"21","author":"JH Strickler","year":"2025","unstructured":"Strickler JH, Bekaii-Saab T, Cercek A, et al. MOUNTAINEER-03: phase III study of first-line tucatinib, trastuzumab, and mFOLFOX6 for HER2-positive metastatic colorectal cancer. Future Oncol. 2025;21:303\u201311.","journal-title":"Future Oncol"},{"key":"1564_CR31","unstructured":"Japanese Society for Cancer of the Colon and Rectum. Guideline-related latest information: trastuzumab deruxtecan therapy for HER2-positive unresectable advanced or recurrent colorectal cancer. April 2026. Available at: https:\/\/www.jsccr.jp\/guideline\/news\/202604_02.html. Accessed July 7, 2026."},{"key":"1564_CR32","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1002\/cncr.31125","volume":"124","author":"JS Ross","year":"2018","unstructured":"Ross JS, Fakih M, Ali SM, et al. Targeting HER2 in colorectal cancer: the landscape of amplification and short variant mutations in ERBB2 and ERBB3. Cancer. 2018;124:1358\u201373.","journal-title":"Cancer"}],"container-title":["Journal of Gastrointestinal Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-026-01564-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12029-026-01564-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-026-01564-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:16:16Z","timestamp":1787922976000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12029-026-01564-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1564"],"URL":"https:\/\/doi.org\/10.1007\/s12029-026-01564-1","relation":{},"ISSN":["1941-6636"],"issn-type":[{"value":"1941-6636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"assertion":[{"value":"17 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics Approval and Consent to Participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Tamotsu Sagawa has received lecture fees from pharmaceutical companies. Hiroyuki Nagashima and Koshi Fujikawa declare no competing\u00a0interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent for Publication","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"200"}}