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Oncol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the risk factors, underlying mechanisms, and preventive strategies associated with hyperprogressive disease (HPD) induced by immunotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the clinical data of a patient who developed HPD following palliative gastrectomy and received a combination therapy of Sintilimab, S-1 (tegafur, gimeracil, and oteracil potassium), and Oxaliplatin (SOX). Additionally, a literature review on tumor immunotherapy was conducted to further explore the risk factors and mechanisms of HPD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this case, the development of HPD was associated with a high postoperative tumor burden, elevated PD-1 expression, and aberrant activation of signaling pathways mediated by EGFR, MET, and FGFR1 amplifications. In addition, a TP53 p.F270V mutation led to inactivation of tumor suppressor function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in cancer treatment, HPD induced by ICIs can drastically shorten patients\u2019 OS, warranting cautious use in populations with high-risk factors. Effective prevention of HPD involves screening for risk factors, monitoring predictive biomarkers such as circulating-free DNA (cfDNA) via liquid biopsy, and identifying high-risk populations through gene mutation analysis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1494007","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T04:11:11Z","timestamp":1749701471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hyperprogression disease induced by Sintilimab combined with Oxaliplatin and S-1 after surgery: a case report and literature review"],"prefix":"10.3389","volume":"15","author":[{"given":"Yaoqi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglou","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","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 Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-023-14569-y","article-title":"Neoadjuvant chemotherapy improves oncological outcomes and long-term survival among elderly patients with locally advanced gastric cancer: A propensity score matched analysis","volume":"31","author":"Rawicz-Pruszy\u0144ski","year":"2024","journal-title":"Ann Surg Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.19918","article-title":"Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer: the ORIENT-16 randomized clinical trial","volume":"330","author":"Xu","year":"2023","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.10.274","article-title":"139MO Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus chemo as first-line (1L) treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC\/GEJC): Final analysis results of the RATIONALE-305 study","volume":"34","author":"Xu","year":"2023","journal-title":"Ann Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1595","article-title":"Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma","volume":"17","author":"Lipson","year":"2011","journal-title":"Clin Cancer Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/science.342.6165.1432","article-title":"Breakthrough of the year 2013. 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