CASE REPORT article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicPrecision Medicine and Targeted Therapies in Gastrointestinal and Genitourinary Solid TumorsView all 23 articles
Spatiotemporal HER2 Heterogeneity in AFP-Producing Gastric Cancer: Navigating Long-Term Survival with Molecularly-Guided Therapy in a Refractory Case
Provisionally accepted
- Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology., shenyang, China
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Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare, aggressive subtype with poor prognosis. We report a metastatic AFPGC case showing spatiotemporal human epidermal growth factor receptor 2 (HER2) heterogeneity. Following progression on first-line FLOT chemotherapy, the 65-year-old male received second-line apatinib plus programmed death-1 (PD-1) inhibitor. At progression (27 months), a lymph node biopsy revealed HER2 conversion from 1+ to 3+. Third-line anti-HER2 antibody-drug conjugate (ADC) DP303c rapidly achieved partial response with normalized AFP. Despite treatment discontinuation due to neurotoxicity after 5 cycles, response persisted. Overall survival reached 79 months. This case highlights: 1) efficacy of anti-angiogenic and immunotherapy in AFPGC; 2) necessity of re-biopsy for detecting HER2 heterogeneity; and 3) potent activity of ADCs against HER2-converted metastases, enabling remarkable survival through sequential precision therapy.
Keywords: heterogeneity, Alpha-fetoprotein-producing gastric cancer, Human epidermal growthfactor receptor 2, Immunotherapy, Anti-angiogenesis therapy
Received: 31 Aug 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Diao, Yin, Sun, Dong and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qian Dong
Jingdong Zhang
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