Cancers, Vol. 12, Pages 2801: Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma: A Systematic Review

Cancers, Vol. 12, Pages 2801: Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma: A Systematic Review Cancers doi: 10.3390/cancers12102801 Authors: Ilaria Proietti Nevena Skroza Nicoletta Bernardini Ersilia Tolino Veronica Balduzzi Anna Marchesiello Simone Michelini Salvatore Volpe Alessandra Mambrin Giorgio Mangino Giovanna Romeo Patrizia Maddalena Catherine Rees Concetta Potenza This systematic review investigated the literature on acquired v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor resistance in patients with melanoma. We searched MEDLINE for articles on BRAF inhibitor resistance in patients with melanoma published since January 2010 in the following areas: (1) genetic basis of resistance; (2) epigenetic and transcriptomic mechanisms; (3) influence of the immune system on resistance development; and (4) combination therapy to overcome resistance. Common resistance mutations in melanoma are BRAF splice variants, BRAF amplification, neuroblastoma RAS viral oncogene homolog (NRAS) mutations and mitogen-activated protein kinase kinase 1/2 (MEK1/2) mutations. Genetic and epigenetic changes reactivate previously blocked mitogen-activated protein kinase (MAPK) pathways, activate alternative signaling pathways, and cause epithelial-to-mesenchymal transition. Once BRAF inhibitor resistance develops, the tumor microenvironment reverts to a low immunogenic state secondary to the induction of programmed cell death ligand...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research