ArticleFrontiers in immunology2025
Case report: Spatiotemporal HER2 heterogeneity in AFP-producing gastric cancer: navigating long-term survival with molecularly-guided therapy in a refractory case.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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