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HER2-targeting agents have been incorporated into the treatment paradigms for HER2-overexpressing breast and gastric cancer. More recently, these agents have shown promise in other gastrointestinal malignancies, such as colon cancer and biliary tract tumors. This study discusses two patients with gallbladder carcinoma and a third with ampullary carcinoma who were able to achieve marked responses to HER2-directed therapy. These cases underscore the importance of molecular analysis for HER2 amplification\/HER2 overexpression, irrespective of tumor histology, and highlight a need for further investigation of HER2-directed therapy beyond breast and gastroesophageal cancers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key Points<\/jats:title>\n               <\/jats:sec>","DOI":"10.1002\/onco.13800","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T12:18:32Z","timestamp":1619353112000},"page":"640-646","source":"Crossref","is-referenced-by-count":14,"title":["Prolonged Response to HER2-Directed Therapy in Three Patients with HER2-Amplified Metastatic Carcinoma of the Biliary System: Case Study and Review of the Literature"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-4655","authenticated-orcid":false,"given":"Michael","family":"May","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Columbia University Irving Medical Center and New York Presbyterian Hospital, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5645-2629","authenticated-orcid":false,"given":"Alexander G.","family":"Raufi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Columbia University Irving Medical Center and New York Presbyterian Hospital, New York, New York, USA"},{"name":"Division of Hematology-Oncology, Lifespan Cancer Institute, Warren-Alpert Medical School of Brown University, Providence, Rhode Island, 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