{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:26:40Z","timestamp":1789770400551,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MEDnoTE srl (Spin-off \u2013 University of Trieste )","award":["Mozart Mednote 01072019"],"award-info":[{"award-number":["Mozart Mednote 01072019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Precision medicine is based on molecular and genotypic patient characterization to define specific target treatment. BRAF mutation is an oncogenic driver, and the Cancer Genome Atlas has identified BRAF mutations in different cancer types. Tumor type agnostic therapy is based on targeting genomic alterations, regardless of tumor origin. In this context, novel therapeutic agents including BRAF and MEK inhibitors based on the molecular landscape in solid tumors have been investigated. Case presentation, Case 1: The first case is chemotherapy-refractory, BRAF V600E mutated intrahepaticcholangiocarcinoma treated with vemurafenib and cobimetinib as third line therapy. In this setting the dual BRAF and MEK inhibition resulted in improved progression-free survival and quality of life; Case 2: The second case shows aBRAF G466A mutated Bellini duct carcinoma (BDC), treated with dabrafenib and trametinib in second line therapy. The disease remained under control for 11 months after the first relapse. Discussion: In the literature there is strong evidence that melanoma, colorectal cancer, non small cell lung cancer and anaplastic thyroid cancer with BRAF mutations are good targets for BRAF\/MEK pathway inhibitors. The VE-BASKET and ROAR basket trials explored the efficacy of vemurafenib and the combination of dabrafenib\/trametinib, respectively, in BRAF V600 mutation-positive cancers other than melanoma, papillary thyroid cancer, colorectal cancer and non small cell lung cancer. Within the concept of tumor type agnostic therapy, we decided to treat our BRAF-mutated tumors with the association of BRAF and MEK inhibitors. Conclusions: Our results confirm the emerging importance of molecular tumor profiling for the successful management of cancer, and the potential of BRAF-targeted therapy in the treatment of rare solid tumors with poor prognosis and no clinical benefit from systemic therapies with.<\/jats:p>","DOI":"10.3390\/ph14020159","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T08:09:09Z","timestamp":1613462949000},"page":"159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature"],"prefix":"10.3390","volume":"14","author":[{"given":"Ottavia","family":"Bernocchi","sequence":"first","affiliation":[{"name":"Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Sirico","sequence":"additional","affiliation":[{"name":"Breast Cancer Unit and Translational Research Unit, Azienda Socio-Sanitaria Territoriale Cremona, Viale Concordia 1, 26100 Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4971-1076","authenticated-orcid":false,"given":"Silvia Paola","family":"Corona","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Strina","sequence":"additional","affiliation":[{"name":"Breast Cancer Unit and Translational Research Unit, Azienda Socio-Sanitaria Territoriale Cremona, Viale Concordia 1, 26100 Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Milani","sequence":"additional","affiliation":[{"name":"Breast Cancer Unit and Translational Research Unit, Azienda Socio-Sanitaria Territoriale Cremona, Viale Concordia 1, 26100 Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosa","family":"Cappelletti","sequence":"additional","affiliation":[{"name":"Breast Cancer Unit and Translational Research Unit, Azienda Socio-Sanitaria Territoriale Cremona, Viale Concordia 1, 26100 Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Azienda Socio-Sanitaria Territoriale Cremona, Viale Concordia 1, 26100 Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Ziglioli","sequence":"additional","affiliation":[{"name":"Breast Cancer Unit and Translational Research Unit, Azienda Socio-Sanitaria Territoriale Cremona, Viale Concordia 1, 26100 Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Cervoni","sequence":"additional","affiliation":[{"name":"Breast Cancer Unit and Translational Research Unit, Azienda Socio-Sanitaria Territoriale Cremona, Viale Concordia 1, 26100 Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Macchiavelli","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, Azienda Socio-Sanitaria Territoriale Cremona, Viale Concordia 1, 26100 Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-8237","authenticated-orcid":false,"given":"Giandomenico","family":"Roviello","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6002-1530","authenticated-orcid":false,"given":"Daniele","family":"Generali","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy"},{"name":"Breast Cancer Unit and Translational Research Unit, Azienda Socio-Sanitaria Territoriale Cremona, Viale Concordia 1, 26100 Cremona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3322\/caac.21560","article-title":"The current state of molecular testing in the treatment of patients with solid tumors, 2019","volume":"69","author":"Goldberg","year":"2019","journal-title":"CA Cancer J. 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