{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:07:10Z","timestamp":1789103230150,"version":"build-2803163510"},"reference-count":83,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Advanced gastroesophageal adenocarcinoma (GEA) carries a poor prognosis, with median overall survival of 13\u201320 months despite standard chemotherapy. Since trastuzumab\u2019s approval, biomarker-driven precision therapies have expanded rapidly. This review comprehensively summarises current and emerging targeted agents across the key molecular targets driving advanced GEA. Methods: A comprehensive literature review was conducted using PubMed, Google Scholar and Cochrane Library in accordance with PRISMA guidelines, searching English-language human studies published between February and July 2026, supplemented by updates during editing to reflect current standards. Results: HER2-directed therapy has progressed from trastuzumab through dual blockade, immunotherapy combinations, next-generation ADCs (notably trastuzumab deruxtecan) and bispecific antibodies such as zanidatamab, which has now overtaken trastuzumab in the first-line setting. CLDN18.2-targeted zolbetuximab has demonstrated survival benefit in biomarker-selected patients, with newer ADCs, BiTEs and the first approved solid-tumour CAR-T therapy (satricabtagene autoleucel) extending this target further. VEGFR2 inhibition with ramucirumab remains a cornerstone in later lines, while novel VEGF\/PD-1(L1) bispecifics are under investigation. FGFR2b-targeted bemarituzumab showed early promise that weakened on phase 3 confirmation, and MET\/EGFR-directed agents, including savolitinib and amivantamab, require stringent biomarker selection to demonstrate benefit amid tumour heterogeneity. Conclusions: Novel targeted agents, particularly to HER2 and CLDN18.2, have demonstrated survival benefit despite ongoing challenges. Other lines are more investigational.<\/jats:p>","DOI":"10.3390\/ph19091420","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:51:48Z","timestamp":1788871908000},"page":"1420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Current and Emerging Targeted Therapy in Advanced Gastroesophageal Adenocarcinoma"],"prefix":"10.3390","volume":"19","author":[{"given":"Oliver","family":"Oakley","sequence":"first","affiliation":[{"name":"Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umair","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Hilltops Medical Centre, Kensington Dr, Great Holm, Milton Keynes MK8 9HN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Smyth","sequence":"additional","affiliation":[{"name":"Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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