A lentiviral vector-based insertional mutagenesis screen identifies mechanisms of resistance to MAPK inhibitors in melanoma.

The treatment of melanoma patients has been revolutionized by the development of targeted therapies such as BRAF and MEK inhibitors which have achieved response rates above 50% and median overall survival of more than 12 months. Similarly, immunotherapies such as checkpoint inhibitors have been used to obtain response rates of up to 70%, with a proportion of patients having long-term durable responses (Luke et al., 2017). Despite these advances, the majority of melanoma patients cannot be cured with available treatments. In those patients that initially respond to targeted therapies, relapse may be driven by the emergence of drug-resistant tumor clones. Recent efforts have shed some light on the mechanisms of resistance to targeted therapies in melanoma (Kong et al., 2017; Krepler et al., 2016; Lu et al., 2017), but there is still a compelling need to catalogue and understand these changes so as to better schedule treatments and improve patient outcomes. This article is protected by copyright. All rights reserved.