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Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature

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 targetin...

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Autores principales: Bernocchi, Ottavia, Sirico, Marianna, Corona, Silvia Paola, Strina, Carla, Milani, Manuela, Cappelletti, Maria Rosa, Ferrero, Giuseppina, Ziglioli, Nicoletta, Cervoni, Valeria, Macchiavelli, Andrea, Roviello, Giandomenico, Generali, Daniele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920250/
https://www.ncbi.nlm.nih.gov/pubmed/33669326
http://dx.doi.org/10.3390/ph14020159
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author Bernocchi, Ottavia
Sirico, Marianna
Corona, Silvia Paola
Strina, Carla
Milani, Manuela
Cappelletti, Maria Rosa
Ferrero, Giuseppina
Ziglioli, Nicoletta
Cervoni, Valeria
Macchiavelli, Andrea
Roviello, Giandomenico
Generali, Daniele
author_facet Bernocchi, Ottavia
Sirico, Marianna
Corona, Silvia Paola
Strina, Carla
Milani, Manuela
Cappelletti, Maria Rosa
Ferrero, Giuseppina
Ziglioli, Nicoletta
Cervoni, Valeria
Macchiavelli, Andrea
Roviello, Giandomenico
Generali, Daniele
author_sort Bernocchi, Ottavia
collection PubMed
description 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.
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spelling pubmed-79202502021-03-02 Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature Bernocchi, Ottavia Sirico, Marianna Corona, Silvia Paola Strina, Carla Milani, Manuela Cappelletti, Maria Rosa Ferrero, Giuseppina Ziglioli, Nicoletta Cervoni, Valeria Macchiavelli, Andrea Roviello, Giandomenico Generali, Daniele Pharmaceuticals (Basel) Case Report 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. MDPI 2021-02-16 /pmc/articles/PMC7920250/ /pubmed/33669326 http://dx.doi.org/10.3390/ph14020159 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Bernocchi, Ottavia
Sirico, Marianna
Corona, Silvia Paola
Strina, Carla
Milani, Manuela
Cappelletti, Maria Rosa
Ferrero, Giuseppina
Ziglioli, Nicoletta
Cervoni, Valeria
Macchiavelli, Andrea
Roviello, Giandomenico
Generali, Daniele
Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature
title Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature
title_full Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature
title_fullStr Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature
title_full_unstemmed Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature
title_short Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature
title_sort tumor type agnostic therapy carrying braf mutation: case reports and review of literature
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920250/
https://www.ncbi.nlm.nih.gov/pubmed/33669326
http://dx.doi.org/10.3390/ph14020159
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