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Cell Cycle Regulation and Melanoma

  • Melanoma (RJ Sullivan, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

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.

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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

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Authors and Affiliations

  1. Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia

    Wen Xu & Grant McArthur

  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia

    Grant McArthur

  3. Molecular Oncology Laboratory, Oncogenic Signalling and Growth Control Program, East Melbourne, Australia

    Grant McArthur

  4. Translational Research Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia

    Grant McArthur

  5. Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Australia

    Grant McArthur

  6. Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett Street, Melbourne, VIC, 8006, Australia

    Grant McArthur

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  1. Wen Xu
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Correspondence to Grant McArthur.

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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.

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Xu, W., McArthur, G. Cell Cycle Regulation and Melanoma. Curr Oncol Rep 18, 34 (2016). https://doi.org/10.1007/s11912-016-0524-y

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