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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

Abstract

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.

Keywords

Metastatic melanoma Cell cycle regulation CDK4/6 inhibitors G1-S checkpoint G2-M checkpoint WEE1 Chk1 MK2 Anti-mitotic agents 

Abbreviations

ATM

Ataxia telangiectasia mutated

ATR

Ataxia telangiectasia and Rad3-related

AURKA

Aurora kinase A

AURKB

Aurora kinase B

CDK 2

Cyclin-dependent kinase 2

CDK1

Cyclin-dependent kinase 1

CDK4/6

Cyclin-dependent kinase 4/6

CDKN2A

Cyclin-dependent kinase inhibitor 2A gene

CHK1

Checkpoint kinase 1

CHK2

Checkpoint kinase 2

E2F

E2F transcription factors

MK2

Mitogen-activated protein kinase-activated protein kinase 2

p16INK4A

Cyclin-dependent inhibitory protein p16INK4A

P21cip1

Cyclin-dependent inhibitory protein P21cip1

P27kip1

Cyclin-dependent inhibitory protein P27kip1

p38

p38 mitogen-activated protein kinase

PLK1

Polo-like kinase 1

RB

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

WEE1 kinase

Notes

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

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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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