Frontiers in oncology · 2026
Case Report: Patient-derived organoids guiding dabrafenib-trametinib therapy in BRAFV600E-mutant metastatic gastric cancer.
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Gong Caifeng, Yang Yang, Yan Qi, Zhao Weiting, Zhang Minghao, Zhang Wen, You Shuhui, Yin Ruihong, Huang Yang, Zhao Yunshan, Zhou Aiping
Аннотация
BACKGROUND: BRAFV600E mutations occur in approximately 0.4% of gastric cancer (GC) cases and are associated with aggressive disease and limited therapeutic options. Cytotoxic chemotherapy remains the standard first-line treatment for this rare molecular subtype, while evidence-based targeted strategies are lacking. Patient-derived organoids (PDOs) have emerged as a functional platform for precision oncology, but their clinical utility in BRAFV600E-mutant GC remains largely unexplored.
CASE PRESENTATION: A patient with rapidly progressive BRAFV600E-mutant metastatic GC presented with mediastinal invasion and malignant pleural effusion, posing a diagnostic challenge in distinguishing metastatic GC from a primary thoracic malignancy. Concordant histopathologic and genomic profiling across multiple tumor sites ultimately confirmed a gastric origin. Despite standard chemotherapy and immunotherapy, the disease progressed rapidly. Patient-derived organoids (PDOs) were established from malignant pleural effusion and used for functional drug sensitivity testing, which demonstrated marked sensitivity to dual BRAF-MEK inhibition. Based on these findings, the patient was treated with dabrafenib plus trametinib, resulting in prompt symptomatic improvement and radiologic regression of pleural effusion and ascites, consistent with PDO-predicted response.
CONCLUSION: This case suggests that dual BRAF-MEK inhibition may represent a feasible precision treatment option for patients with BRAFV600E-mutant GC lacking established targeted therapies. Moreover, it highlights the potential role of PDOs as a functional decision-support platform for guiding individualized treatment selection in rare, genomically defined GC subtypes.
CASE PRESENTATION: A patient with rapidly progressive BRAFV600E-mutant metastatic GC presented with mediastinal invasion and malignant pleural effusion, posing a diagnostic challenge in distinguishing metastatic GC from a primary thoracic malignancy. Concordant histopathologic and genomic profiling across multiple tumor sites ultimately confirmed a gastric origin. Despite standard chemotherapy and immunotherapy, the disease progressed rapidly. Patient-derived organoids (PDOs) were established from malignant pleural effusion and used for functional drug sensitivity testing, which demonstrated marked sensitivity to dual BRAF-MEK inhibition. Based on these findings, the patient was treated with dabrafenib plus trametinib, resulting in prompt symptomatic improvement and radiologic regression of pleural effusion and ascites, consistent with PDO-predicted response.
CONCLUSION: This case suggests that dual BRAF-MEK inhibition may represent a feasible precision treatment option for patients with BRAFV600E-mutant GC lacking established targeted therapies. Moreover, it highlights the potential role of PDOs as a functional decision-support platform for guiding individualized treatment selection in rare, genomically defined GC subtypes.