Cell Cycle Regulation and Melanoma
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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.
KeywordsMetastatic melanoma Cell cycle regulation CDK4/6 inhibitors G1-S checkpoint G2-M checkpoint WEE1 Chk1 MK2 Anti-mitotic agents
Ataxia telangiectasia mutated
Ataxia telangiectasia and Rad3-related
Aurora kinase A
Aurora kinase B
- CDK 2
Cyclin-dependent kinase 2
Cyclin-dependent kinase 1
Cyclin-dependent kinase 4/6
Cyclin-dependent kinase inhibitor 2A gene
Checkpoint kinase 1
Checkpoint kinase 2
E2F transcription factors
Mitogen-activated protein kinase-activated protein kinase 2
Cyclin-dependent inhibitory protein p16INK4A
Cyclin-dependent inhibitory protein P21cip1
Cyclin-dependent inhibitory protein P27kip1
p38 mitogen-activated protein kinase
Polo-like kinase 1
- Restriction point
A point in G1 of the cell cycle at which the cell becomes committed to cycling, marking the transition from growth factor-dependent to growth factor-independent cell cycle progression
Compliance with Ethical Standard
Conflict of Interest
Wen Xu declares that he has no conflict of interest.
Grant McArthur has received financial support through grants from Pfizer, Celgene, and Ventana Medical Systems, and has served as a consultant for Provectus Biopharmaceuticals.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References of special interest published within the last 2 years have been highlights as: • Of importance •• Of major importance
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