{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:17:49Z","timestamp":1783073869607,"version":"3.54.6"},"reference-count":156,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Esophageal cancer is a globally prevalent malignancy with poor clinical outcomes. Chemotherapy remains an effective strategy for esophageal cancer. However, its effectiveness is substantially limited by chemoresistance, which arises from both tumor cell adaptation and changes in the surrounding microenvironment. In light of these challenges, combination strategies show great promise for overcoming chemoresistance. Notably, the integration of chemotherapy with PD-1\/PD-L1 blockade has demonstrated substantial survival benefits across multiple phase III clinical trials. This review provides a comprehensive overview of the mechanisms underlying chemotherapy resistance in esophageal cancer. More importantly, we summarize the current advances in chemotherapy-based combination therapies, as well as nanoparticle\u2212based delivery systems and antibody\u2212drug conjugates. These advances reinforce the potential for developing more effective therapeutic strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1784325","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:06:55Z","timestamp":1780466815000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Overcoming chemoresistance in esophageal cancer with synergistic strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Chunxiao","family":"Gao","sequence":"first","affiliation":[{"name":"Zhengzhou Key Laboratory of Lipid Metabolism and Precision Diagnosis & Treatment in Oncology, Oncology Department, the Fifth Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]},{"name":"State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences","place":["Zhengzhou, China"]},{"name":"Marshall B. J. 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