Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy
The University of Sydney · University of California, Los Angeles · +4 more institutions
Abstract
Abstract BRAF inhibitors elicit rapid antitumor responses in the majority of patients with BRAFV600-mutant melanoma, but acquired drug resistance is almost universal. We sought to identify the core resistance pathways and the extent of tumor heterogeneity during disease progression. We show that mitogen-activated protein kinase reactivation mechanisms were detected among 70% of disease-progressive tissues, with RAS mutations, mutant BRAF amplification, and alternative splicing being most common. We also detected PI3K–PTEN–AKT–upregulating genetic alterations among 22% of progressive melanomas. Distinct molecular lesions in both core drug escape pathways were commonly detected concurrently in the same tumor or…
Citation impact
- FWCI
- 38.58
- Percentile
- 100%
- References
- 53
Authors
19- HSHubing Shi
The University of Sydney, University of California, Los Angeles, Ludwig Cancer Research, Westmead Hospital, UCLA Jonsson Comprehensive Cancer Center, Vanderbilt University Medical Center
- WHWilly Hugo
The University of Sydney, University of California, Los Angeles, Ludwig Cancer Research, Westmead Hospital, UCLA Jonsson Comprehensive Cancer Center, Vanderbilt University Medical Center
- XKXiangju Kong
The University of Sydney, University of California, Los Angeles, Ludwig Cancer Research, Westmead Hospital, UCLA Jonsson Comprehensive Cancer Center, Vanderbilt University Medical Center
- AHAayoung Hong
The University of Sydney, University of California, Los Angeles, Ludwig Cancer Research, Westmead Hospital, UCLA Jonsson Comprehensive Cancer Center, Vanderbilt University Medical Center
- RCRichard C. Koya
The University of Sydney, University of California, Los Angeles, Ludwig Cancer Research, Westmead Hospital, UCLA Jonsson Comprehensive Cancer Center, Vanderbilt University Medical Center
Topics & keywords
- Melanoma
- Resistance (ecology)
- Cancer research
- Medicine
- Acquired resistance
- Biology
- Drug resistance
- Computational biology
- Good health and well-being