The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma
Broad Institute · Heidelberg University · +9 more institutions
Abstract
Abstract Most patients with BRAFV600-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole-exome sequencing on formalin-fixed, paraffin-embedded tumors from 45 patients with BRAFV600-mutant metastatic melanoma who received vemurafenib or dabrafenib monotherapy. Genetic alterations in known or putative RAF inhibitor resistance genes were observed in 23 of 45 patients (51%). Besides previously characterized alterations, we discovered a “long tail” of new mitogen-activated protein kinase (MAPK) pathway alterations (MAP2K2, MITF) that…
Citation impact
- FWCI
- 38.73
- Percentile
- 100%
- References
- 54
Authors
32- EMEliezer M. Van AllenCorresponding
Broad Institute, Heidelberg University, University Hospital Heidelberg, Massachusetts General Hospital, Harvard–MIT Division of Health Sciences and Technology, Dana-Farber Cancer Institute, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
- NWNikhil Wagle
Broad Institute, Heidelberg University, University Hospital Heidelberg, Massachusetts General Hospital, Harvard–MIT Division of Health Sciences and Technology, Dana-Farber Cancer Institute, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
- ASAntje Sucker
Broad Institute, Heidelberg University, University Hospital Heidelberg, Massachusetts General Hospital, Harvard–MIT Division of Health Sciences and Technology, Dana-Farber Cancer Institute, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
- DJDaniel J. Treacy
Broad Institute, Heidelberg University, University Hospital Heidelberg, Massachusetts General Hospital, Harvard–MIT Division of Health Sciences and Technology, Dana-Farber Cancer Institute, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
- CMCory M. Johannessen
Broad Institute, Heidelberg University, University Hospital Heidelberg, Massachusetts General Hospital, Harvard–MIT Division of Health Sciences and Technology, Dana-Farber Cancer Institute, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
Topics & keywords
- Dabrafenib
- Vemurafenib
- Trametinib
- Cancer research
- Melanoma
- MEK inhibitor
- Mutant
- Biology
- Good health and well-being