TY - JOUR
T1 - Novel Targeted Therapies for Metastatic Melanoma
AU - Iams, Wade T.
AU - Sosman, Jeffrey A.
AU - Chandra, Sunandana
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Oncogene-targeted therapy is a major component of precision oncology, and although patients with metastatic melanoma have experienced improved outcomes with this strategy, there are a number of potential therapeutic targets currently under study that may further increase the drug armamentarium for this patient population. In this review, we discuss the landscape of targeted therapies for patients with advanced melanoma, focusing on oncogene mutation-specific targets. In patients with typical BRAF V600-mutant melanoma, combination BRAF and MEK inhibition has surpassed outcomes compared with monotherapy with BRAF or MEK inhibition alone, and current strategies seek to address inevitable resistance mechanisms. For patients with NRAS-mutant melanoma, MEK inhibitor monotherapy and combined MEK and CDK4/6 inhibition are burgeoning strategies; for patients with KIT-mutant melanoma, tyrosine kinase inhibition is being leveraged, and for NF-1-mutant melanoma, mTOR and MEK inhibition is being actively evaluated. In patients with atypical, non-V600 BRAF-mutant melanoma, MEK inhibitor monotherapy is the potential novel targeted approach on the horizon. For advanced uveal melanoma, novel targets such as IMCgp100 and glembatumumab have shown activity in early studies. We review additional strategies that remain in the preclinical and early clinical pipeline, so there is much hope for the future of targeted agents for distinct molecular cohorts of patients with advanced melanoma.
AB - Oncogene-targeted therapy is a major component of precision oncology, and although patients with metastatic melanoma have experienced improved outcomes with this strategy, there are a number of potential therapeutic targets currently under study that may further increase the drug armamentarium for this patient population. In this review, we discuss the landscape of targeted therapies for patients with advanced melanoma, focusing on oncogene mutation-specific targets. In patients with typical BRAF V600-mutant melanoma, combination BRAF and MEK inhibition has surpassed outcomes compared with monotherapy with BRAF or MEK inhibition alone, and current strategies seek to address inevitable resistance mechanisms. For patients with NRAS-mutant melanoma, MEK inhibitor monotherapy and combined MEK and CDK4/6 inhibition are burgeoning strategies; for patients with KIT-mutant melanoma, tyrosine kinase inhibition is being leveraged, and for NF-1-mutant melanoma, mTOR and MEK inhibition is being actively evaluated. In patients with atypical, non-V600 BRAF-mutant melanoma, MEK inhibitor monotherapy is the potential novel targeted approach on the horizon. For advanced uveal melanoma, novel targets such as IMCgp100 and glembatumumab have shown activity in early studies. We review additional strategies that remain in the preclinical and early clinical pipeline, so there is much hope for the future of targeted agents for distinct molecular cohorts of patients with advanced melanoma.
KW - BRAF inhibition
KW - MEK inhibition
KW - melanoma
KW - novel targeted therapy
KW - oncogene-targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85011554570&partnerID=8YFLogxK
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U2 - 10.1097/PPO.0000000000000242
DO - 10.1097/PPO.0000000000000242
M3 - Review article
C2 - 28114255
AN - SCOPUS:85011554570
SN - 1528-9117
VL - 23
SP - 54
EP - 58
JO - Cancer Journal (United States)
JF - Cancer Journal (United States)
IS - 1
ER -