Cell Cycle Regulation and Melanoma

  • Wen Xu
  • Grant McArthur
Melanoma (RJ Sullivan, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Melanoma


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.


Metastatic 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


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


Retinoblastoma protein

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


WEE1 kinase


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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Medical OncologyPeter MacCallum Cancer CentreEast MelbourneAustralia
  2. 2.Sir Peter MacCallum Department of OncologyUniversity of MelbourneParkvilleAustralia
  3. 3.Molecular Oncology LaboratoryOncogenic Signalling and Growth Control ProgramEast MelbourneAustralia
  4. 4.Translational Research Laboratory, Cancer Therapeutics ProgramPeter MacCallum Cancer CentreEast MelbourneAustralia
  5. 5.Peter MacCallum Cancer CentreUniversity of MelbourneEast MelbourneAustralia
  6. 6.Research DivisionPeter MacCallum Cancer CentreMelbourneAustralia

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