MEK inhibitors for the treatment of immunotherapy-resistant, AGK-BRAF fusion advanced acral melanoma: a case report and literature review
Abstract Purpose Acral melanoma (AM), a rare and aggressive melanoma subtype with poor prognosis, presents unique challenges in treatment due to its distinct molecular and immune characteristics. This case report describes a patient with AM harboring an AGK-BRAF fusion mutation, aiming to explore po...
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| Format: | Article |
| Language: | English |
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Springer
2025-04-01
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| Series: | Journal of Cancer Research and Clinical Oncology |
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| Online Access: | https://doi.org/10.1007/s00432-025-06083-3 |
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| author | Yanling Zhang Xifeng Zhang Weikang Shao Ji Gao Mei Xiang Yan Wang Mengmeng Liu Weizhen Zhang Xianbin Liang |
| author_facet | Yanling Zhang Xifeng Zhang Weikang Shao Ji Gao Mei Xiang Yan Wang Mengmeng Liu Weizhen Zhang Xianbin Liang |
| author_sort | Yanling Zhang |
| collection | DOAJ |
| description | Abstract Purpose Acral melanoma (AM), a rare and aggressive melanoma subtype with poor prognosis, presents unique challenges in treatment due to its distinct molecular and immune characteristics. This case report describes a patient with AM harboring an AGK-BRAF fusion mutation, aiming to explore potential mechanisms of resistance to current treatment modalities. Methods We analyzed tumor tissue samples from the primary and metastatic lesions of the patient using next-generation sequencing (NGS) for genomic profiling and multiplex immunohistochemistry (mIHC) to assess the immune microenvironment. The patient underwent multiple lines of treatment, including immunotherapy, chemotherapy, and targeted therapy, with their clinical outcomes documented and evaluated. Results The AGK-BRAF fusion mutation and its reciprocal BRAF-AGK rearrangement were identified in both primary and metastatic tumors. Immune profiling revealed abundant CD8 + T cells, PD-L1 + cells, and CD68 + macrophages localized predominantly in the tumor interstitial region, potentially explaining the poor response to immunotherapy. Despite initial disease stabilization with trametinib and lenvatinib, rapid progression occurred, highlighting tumor heterogeneity and limited efficacy of combined therapies. Conclusion This case underscores the need for personalized approaches in treating AM, especially those with rare molecular alterations like AGK-BRAF fusion. Insights from genomic and immune profiling may inform future therapeutic strategies to overcome resistance and improve outcomes in this challenging melanoma subtype. |
| format | Article |
| id | doaj-art-fe4dd15a25b245caaf6fe7ea6f988cf6 |
| institution | Kabale University |
| issn | 1432-1335 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Cancer Research and Clinical Oncology |
| spelling | doaj-art-fe4dd15a25b245caaf6fe7ea6f988cf62025-08-20T03:53:57ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-04-0115141910.1007/s00432-025-06083-3MEK inhibitors for the treatment of immunotherapy-resistant, AGK-BRAF fusion advanced acral melanoma: a case report and literature reviewYanling Zhang0Xifeng Zhang1Weikang Shao2Ji Gao3Mei Xiang4Yan Wang5Mengmeng Liu6Weizhen Zhang7Xianbin Liang8Department of Medical Oncology, The Third People’s Hospital of ZhengzhouDepartment of Medical Oncology, The Third People’s Hospital of ZhengzhouGenecast Biotechnology Co., LtdDepartment of Orthopaedics, The Third People’s Hospital of ZhengzhouDepartment of Medical Oncology, The Third People’s Hospital of ZhengzhouDepartment of Medical Oncology, The Third People’s Hospital of ZhengzhouDepartment of Pathology, The Third People’s Hospital of ZhengzhouDepartment of Medical Oncology, The Third People’s Hospital of ZhengzhouDepartment of Medical Oncology, The Third People’s Hospital of ZhengzhouAbstract Purpose Acral melanoma (AM), a rare and aggressive melanoma subtype with poor prognosis, presents unique challenges in treatment due to its distinct molecular and immune characteristics. This case report describes a patient with AM harboring an AGK-BRAF fusion mutation, aiming to explore potential mechanisms of resistance to current treatment modalities. Methods We analyzed tumor tissue samples from the primary and metastatic lesions of the patient using next-generation sequencing (NGS) for genomic profiling and multiplex immunohistochemistry (mIHC) to assess the immune microenvironment. The patient underwent multiple lines of treatment, including immunotherapy, chemotherapy, and targeted therapy, with their clinical outcomes documented and evaluated. Results The AGK-BRAF fusion mutation and its reciprocal BRAF-AGK rearrangement were identified in both primary and metastatic tumors. Immune profiling revealed abundant CD8 + T cells, PD-L1 + cells, and CD68 + macrophages localized predominantly in the tumor interstitial region, potentially explaining the poor response to immunotherapy. Despite initial disease stabilization with trametinib and lenvatinib, rapid progression occurred, highlighting tumor heterogeneity and limited efficacy of combined therapies. Conclusion This case underscores the need for personalized approaches in treating AM, especially those with rare molecular alterations like AGK-BRAF fusion. Insights from genomic and immune profiling may inform future therapeutic strategies to overcome resistance and improve outcomes in this challenging melanoma subtype.https://doi.org/10.1007/s00432-025-06083-3Acral melanomaAGK-BRAF fusionImmunotherapyTumor immune microenvironmentMEK inhibitors |
| spellingShingle | Yanling Zhang Xifeng Zhang Weikang Shao Ji Gao Mei Xiang Yan Wang Mengmeng Liu Weizhen Zhang Xianbin Liang MEK inhibitors for the treatment of immunotherapy-resistant, AGK-BRAF fusion advanced acral melanoma: a case report and literature review Journal of Cancer Research and Clinical Oncology Acral melanoma AGK-BRAF fusion Immunotherapy Tumor immune microenvironment MEK inhibitors |
| title | MEK inhibitors for the treatment of immunotherapy-resistant, AGK-BRAF fusion advanced acral melanoma: a case report and literature review |
| title_full | MEK inhibitors for the treatment of immunotherapy-resistant, AGK-BRAF fusion advanced acral melanoma: a case report and literature review |
| title_fullStr | MEK inhibitors for the treatment of immunotherapy-resistant, AGK-BRAF fusion advanced acral melanoma: a case report and literature review |
| title_full_unstemmed | MEK inhibitors for the treatment of immunotherapy-resistant, AGK-BRAF fusion advanced acral melanoma: a case report and literature review |
| title_short | MEK inhibitors for the treatment of immunotherapy-resistant, AGK-BRAF fusion advanced acral melanoma: a case report and literature review |
| title_sort | mek inhibitors for the treatment of immunotherapy resistant agk braf fusion advanced acral melanoma a case report and literature review |
| topic | Acral melanoma AGK-BRAF fusion Immunotherapy Tumor immune microenvironment MEK inhibitors |
| url | https://doi.org/10.1007/s00432-025-06083-3 |
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