TY  - JOUR
AU  - Manzano, José Luís
AU  - Layos, Laura
AU  - Bugés, Cristina
AU  - Llanos Gil, María de los
AU  - Vila, Laia
AU  - Martínez-Balibrea, Eva
AU  - Martínez-Cardús, Anna
PY  - 2016
TI  - Resistant mechanisms to BRAF inhibitors in melanoma
JF  - Annals of Translational Medicine; Vol 4, No 12 (June 28, 2016): Annals of Translational Medicine
Y2  - 2016
KW  - 
N2  - Patients with advanced melanoma have traditionally had very poor prognosis. However, since 2011 better understanding of the biology and epidemiology of this disease has revolutionized its treatment, with newer therapies becoming available. These newer therapies can be classified into immunotherapy and targeted therapy. The immunotherapy arsenal includes inhibitors of CTLA4, PD-1 and PDL-1, while targeted therapy focuses on BRAF and MEK. BRAF inhibitors (vemurafenib, dabrafenib) have shown benefit in terms of overall survival (OS) compared to chemotherapy, and their combination with MEK inhibitors has recently been shown to improve progression-free survival (PFS), compared with monotherapy with BRAF inhibitors. However, almost 20% of patients initially do not respond, due to intrinsic resistance to therapy and, of those who do, most eventually develop mechanisms of acquired resistance, including reactivation of the MAP kinase pathway, persistent activation of receptor tyrosine kinase (RTKS) receptor, activation of phosphatidyinositol-3OH kinase, overexpression of epidermal growth factor receptor (EGFR), and interactions with the tumor microenvironment. Herein we comment in detail on mechanisms of resistance to targeted therapy and discuss the strategies to overcome them.
UR  - https://atm.amegroups.org/article/view/10777