TY - JOUR
T1 - BRAF kinase inhibitors for treatment of melanoma
T2 - developments from early-stage animal studies to Phase II clinical trials
AU - Fujimura, Taku
AU - Hidaka, Takanori
AU - Kambayashi, Yumi
AU - Aiba, Setsuya
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Introduction: Approximately, 30.4–66.0% of cutaneous melanomas possess a mutation in the BRAF gene that activates downstream signaling through the mitogen-activated protein (MAP) kinase pathway; this provides an attractive target for the treatment of advanced melanoma. Although BRAF inhibitors rapidly suppress melanoma growth, median progression-free survival remains unsatisfactory. Recent clinical trials have investigated drugs that can optimally enhance and prolong the anti-melanoma effects of BRAF inhibitors. Area covered: This review discusses the development of BRAF inhibitor-based combination therapies for BRAF-mutant advanced melanoma. Expert opinion: Future strategies for the treatment of advanced melanoma include novel combination therapies using BRAF/MEK inhibitors and immune checkpoints inhibitors or histone deacetylase inhibitors. These combination therapies might enhance antitumor responses against melanoma, prolonging survival in advanced melanoma patients. Further clinical studies are needed to optimize these novel combination therapies.
AB - Introduction: Approximately, 30.4–66.0% of cutaneous melanomas possess a mutation in the BRAF gene that activates downstream signaling through the mitogen-activated protein (MAP) kinase pathway; this provides an attractive target for the treatment of advanced melanoma. Although BRAF inhibitors rapidly suppress melanoma growth, median progression-free survival remains unsatisfactory. Recent clinical trials have investigated drugs that can optimally enhance and prolong the anti-melanoma effects of BRAF inhibitors. Area covered: This review discusses the development of BRAF inhibitor-based combination therapies for BRAF-mutant advanced melanoma. Expert opinion: Future strategies for the treatment of advanced melanoma include novel combination therapies using BRAF/MEK inhibitors and immune checkpoints inhibitors or histone deacetylase inhibitors. These combination therapies might enhance antitumor responses against melanoma, prolonging survival in advanced melanoma patients. Further clinical studies are needed to optimize these novel combination therapies.
KW - BRAF inhibitors
KW - BRAF resistance
KW - BRAF-mutant metastatic melanoma
KW - HDAC inhibitors
KW - MEK inhibitors
KW - immune checkpoints inhibitors
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U2 - 10.1080/13543784.2019.1558442
DO - 10.1080/13543784.2019.1558442
M3 - Review article
C2 - 30556435
AN - SCOPUS:85059829102
VL - 28
SP - 143
EP - 148
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
SN - 1354-3784
IS - 2
ER -