Sistema de Salut de Catalunya
Institut Català de la Salut
[Ros J, Baraibar I, Salvà F, Argilés G, Élez E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Sardo E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Mulet N] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Department of Medical Oncology, Institut Català d’Oncologia, Barcelona, Spain. [Martini G, Ciardiello D] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Caserta, Campania, Italy. [Tabernero J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. UVic-UCC, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2022-03-14T12:45:21Z
2022-03-14T12:45:21Z
2021-01
Inhibidor de BRAF; Binimetinib; Cáncer de colon
BRAF inhibitor; Binimetinib; Colon cancer
Inhibidor de BRAF; Binimetinib; Càncer de còlon
Introduction: BRAF driver mutations are found in up to 15% of patients with colorectal cancer (CRC) and lead to constitutive activation of BRAF kinase and sustained RAS/RAF/MEK/ERK pathway signaling. BRAF mutations define a sub-population characterized by a poor prognosis and dismal median survival. Following successful outcomes with BRAF inhibition in BRAF mutant metastatic melanoma, this approach was evaluated in metastatic colorectal cancer (mCRC). The development and combination of targeted therapies against multiple signaling pathways has proved particularly successful, with improved survival and response rates. Areas covered: This review addresses the development of therapeutic strategies with inhibitors targeting MAPK/ERK and EGFR signaling in BRAF V600E mutated mCRC, focusing on encorafenib, binimetinib and cetuximab. A pharmacological and clinical review of these drugs and the therapeutic approaches behind their optimization are presented. Expert opinion: Exploiting knowledge of the mechanisms of resistance to BRAF inhibitors has been crucial to developing effective therapeutic strategies in BRAF-V600E mutant mCRC. The BEACON trial is a successful example of this approach, using encorafenib and cetuximab with or without binimetinib in patients with previously treated BRAF V600E mutant mCRC, showing an impressive improvement in clinical outcomes and tolerable toxicity compared with chemotherapy, establishing a new standard of care in this setting.
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from Instituto de Salud Carlos III (ISCIII) FIS/FEDER (PI17/00947, PI20/00968) and from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 635342.
Article
Published version
English
Còlon - Càncer - Tractament; Recte - Càncer - Tractament; Metàstasi; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica
SAGE Publications
Therapeutic Advances in Medical Oncology;13
https://doi.org/10.1177/1758835921992974
info:eu-repo/grantAgreement/ES/PE2013-2016/PI17%2F00947
info:eu-repo/grantAgreement/ES/PE2017-2020/PI20%2F00968
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
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