Enhanced response to dabrafenib plus trametinib in a patient with BRAFV600E lung cancer harboring an RNF43 variant of unknown significance: a case report
BackgroundLiterature evidence reports that RNF43 (ring finger protein 43) gene mutations could serve as predictive biomarkers of response to certain anti-cancer therapies. To delve deeper into the specific role of RNF43 mutations in lung cancer and their relevance to therapy response, we provide the...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1600457/full |
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| author | Ettore D’Argento Antonio Vitale Antonio Vitale Jacopo Russo Jacopo Russo Angelo Minucci Alessandra Cancellieri Alessio Stefani Alessio Stefani Federico Monaca Federico Monaca Guido Horn Guido Horn Denis Occhipinti Denis Occhipinti Paola Troisi Paola Troisi Alessandro Scala Alessandro Scala Sara Polidori Sara Polidori Francesco D’Argento Mariantonietta Di Salvatore Emilio Bria Emilio Bria Giampaolo Tortora Giampaolo Tortora |
| author_facet | Ettore D’Argento Antonio Vitale Antonio Vitale Jacopo Russo Jacopo Russo Angelo Minucci Alessandra Cancellieri Alessio Stefani Alessio Stefani Federico Monaca Federico Monaca Guido Horn Guido Horn Denis Occhipinti Denis Occhipinti Paola Troisi Paola Troisi Alessandro Scala Alessandro Scala Sara Polidori Sara Polidori Francesco D’Argento Mariantonietta Di Salvatore Emilio Bria Emilio Bria Giampaolo Tortora Giampaolo Tortora |
| author_sort | Ettore D’Argento |
| collection | DOAJ |
| description | BackgroundLiterature evidence reports that RNF43 (ring finger protein 43) gene mutations could serve as predictive biomarkers of response to certain anti-cancer therapies. To delve deeper into the specific role of RNF43 mutations in lung cancer and their relevance to therapy response, we provide the first report of marked efficacy of the dabrafenib and trametinib therapeutic combination in a patient with microsatellite-stable (MSS) non-small-cell lung cancer (NSCLC) with BRAFV600 and RNF43 mutations.Case descriptionAn 85-year-old patient was diagnosed with NSCLC with the presence of MSS, BRAFV600E and RNF43 mutations. The patient started the combination treatment with dabrafenib and trametinib, soon reporting an overall clinical benefit. A contrast-enhanced cranio–thorax–abdomen CT scan performed after 1 month of therapy reported a sharp reduction in lung cancer and hilo-mediastinal lymphadenomegaly; the central colliquation of the left adrenal metastasis was also reported. After 9 months of therapy, the cranio-thorax-abdomen CT scan with contrast medium confirmed the reduction of the adenocarcinoma, with residual scarring component; the right adrenal lesion was not visible, and the contralateral lesion was stable. At the last follow-up (February 2024), the global clinical condition of the patient was good; she was autonomous, and oxygen therapy was not necessary.ConclusionsOur clinical case represents the first report of marked efficacy of the dabrafenib–trametinib combination reported in an 85-year-old patient diagnosed with NSCLC with the presence of MSS, BRAFV600E and RNF43 mutations. This supports the hypothesis on the relevance of RNF43 mutations in predicting the clinical benefit of targeted therapies and in modulating the anti-tumor activity of anti-BRAF therapies, suggesting that RNF43 mutations represent a promising biomarker that warrants further validation for its potential to help prioritize therapy combinations in selected lung cancer patients. |
| format | Article |
| id | doaj-art-a18c26aaa24043d1a9955ad85bafbacc |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-a18c26aaa24043d1a9955ad85bafbacc2025-08-20T03:50:43ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.16004571600457Enhanced response to dabrafenib plus trametinib in a patient with BRAFV600E lung cancer harboring an RNF43 variant of unknown significance: a case reportEttore D’Argento0Antonio Vitale1Antonio Vitale2Jacopo Russo3Jacopo Russo4Angelo Minucci5Alessandra Cancellieri6Alessio Stefani7Alessio Stefani8Federico Monaca9Federico Monaca10Guido Horn11Guido Horn12Denis Occhipinti13Denis Occhipinti14Paola Troisi15Paola Troisi16Alessandro Scala17Alessandro Scala18Sara Polidori19Sara Polidori20Francesco D’Argento21Mariantonietta Di Salvatore22Emilio Bria23Emilio Bria24Giampaolo Tortora25Giampaolo Tortora26Comprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyDepartmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyPathology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyUOC Radiologia e Neuroradiologia, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyMedical Oncology, Ospedale Isola Tiberina – Gemelli Isola, Rome, ItalyComprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, ItalyFaculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyBackgroundLiterature evidence reports that RNF43 (ring finger protein 43) gene mutations could serve as predictive biomarkers of response to certain anti-cancer therapies. To delve deeper into the specific role of RNF43 mutations in lung cancer and their relevance to therapy response, we provide the first report of marked efficacy of the dabrafenib and trametinib therapeutic combination in a patient with microsatellite-stable (MSS) non-small-cell lung cancer (NSCLC) with BRAFV600 and RNF43 mutations.Case descriptionAn 85-year-old patient was diagnosed with NSCLC with the presence of MSS, BRAFV600E and RNF43 mutations. The patient started the combination treatment with dabrafenib and trametinib, soon reporting an overall clinical benefit. A contrast-enhanced cranio–thorax–abdomen CT scan performed after 1 month of therapy reported a sharp reduction in lung cancer and hilo-mediastinal lymphadenomegaly; the central colliquation of the left adrenal metastasis was also reported. After 9 months of therapy, the cranio-thorax-abdomen CT scan with contrast medium confirmed the reduction of the adenocarcinoma, with residual scarring component; the right adrenal lesion was not visible, and the contralateral lesion was stable. At the last follow-up (February 2024), the global clinical condition of the patient was good; she was autonomous, and oxygen therapy was not necessary.ConclusionsOur clinical case represents the first report of marked efficacy of the dabrafenib–trametinib combination reported in an 85-year-old patient diagnosed with NSCLC with the presence of MSS, BRAFV600E and RNF43 mutations. This supports the hypothesis on the relevance of RNF43 mutations in predicting the clinical benefit of targeted therapies and in modulating the anti-tumor activity of anti-BRAF therapies, suggesting that RNF43 mutations represent a promising biomarker that warrants further validation for its potential to help prioritize therapy combinations in selected lung cancer patients.https://www.frontiersin.org/articles/10.3389/fonc.2025.1600457/fullnon-small-cell lung cancerdabrafenibtrametinibBRAF V600ERNF4case report |
| spellingShingle | Ettore D’Argento Antonio Vitale Antonio Vitale Jacopo Russo Jacopo Russo Angelo Minucci Alessandra Cancellieri Alessio Stefani Alessio Stefani Federico Monaca Federico Monaca Guido Horn Guido Horn Denis Occhipinti Denis Occhipinti Paola Troisi Paola Troisi Alessandro Scala Alessandro Scala Sara Polidori Sara Polidori Francesco D’Argento Mariantonietta Di Salvatore Emilio Bria Emilio Bria Giampaolo Tortora Giampaolo Tortora Enhanced response to dabrafenib plus trametinib in a patient with BRAFV600E lung cancer harboring an RNF43 variant of unknown significance: a case report Frontiers in Oncology non-small-cell lung cancer dabrafenib trametinib BRAF V600E RNF4 case report |
| title | Enhanced response to dabrafenib plus trametinib in a patient with BRAFV600E lung cancer harboring an RNF43 variant of unknown significance: a case report |
| title_full | Enhanced response to dabrafenib plus trametinib in a patient with BRAFV600E lung cancer harboring an RNF43 variant of unknown significance: a case report |
| title_fullStr | Enhanced response to dabrafenib plus trametinib in a patient with BRAFV600E lung cancer harboring an RNF43 variant of unknown significance: a case report |
| title_full_unstemmed | Enhanced response to dabrafenib plus trametinib in a patient with BRAFV600E lung cancer harboring an RNF43 variant of unknown significance: a case report |
| title_short | Enhanced response to dabrafenib plus trametinib in a patient with BRAFV600E lung cancer harboring an RNF43 variant of unknown significance: a case report |
| title_sort | enhanced response to dabrafenib plus trametinib in a patient with brafv600e lung cancer harboring an rnf43 variant of unknown significance a case report |
| topic | non-small-cell lung cancer dabrafenib trametinib BRAF V600E RNF4 case report |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1600457/full |
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