期刊
CURRENT ONCOLOGY REPORTS
卷 18, 期 6, 页码 -出版社
SPRINGER
DOI: 10.1007/s11912-016-0524-y
关键词
Metastatic melanoma; Cell cycle regulation; CDK4/6 inhibitors; G1-S checkpoint; G2-M checkpoint; WEE1; Chk1; MK2; Anti-mitotic agents
类别
资金
- Pfizer
- Celgene
- Ventana Medical Systems
Dysregulation of cell cycle control is a hallmark of melanomagenesis. Agents targeting the G1-S and G2-M checkpoints, as well as direct anti-mitotic agents, have all shown promising preclinical activity in melanoma. However, in vivo, standalone single agents targeting cell cycle regulation have only demonstrated modest efficacy in unselected patients. The advent of specific CDK 4/6 inhibitors targeting the G1-S transition, with an improved therapeutic index, is a significant step forward. Potential synergy exists with the combination of CDK4/6 inhibitors with existing therapies targeting the MAPK pathway, particularly in subsets of metastatic melanomas such as NRAS and BRAF mutants. This reviews summaries of the latest developments in both preclinical and clinical data with cell cycle-targeted therapies in melanoma.
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