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Review
. 2015 Aug;2(3):255-266.
doi: 10.2217/mmt.15.14. Epub 2015 Aug 10.

CDK4 inhibitors an emerging strategy for the treatment of melanoma

Belinda Lee  1   1 , Grant A McArthur  1   2   3   4   5   1   2   3   4   5
Affiliations
Review

CDK4 inhibitors an emerging strategy for the treatment of melanoma

Belinda Lee et al. Melanoma Manag. 2015 Aug.

Abstract

Research into the cyclin-dependent kinases and their inhibitors is finally coming into the forefront of clinical research in cancer. Targeted therapies such as BRAF inhibitors have led the way in improving treatment outcomes in advanced melanoma. Based on detailed genomic knowledge of melanoma it is now time to extend targeted therapies beyond BRAF to fulfill the vision of precision medicine. The p16INK4A-cyclin D-CDK4/6-retinoblastoma protein pathway (RB pathway) is dysregulated in more than 90% of melanomas and interacts biochemically and genetically with the RAS/RAF/MEK/ERK pathway. Recognizing and understanding these processes that drive melanomagenesis is essential to rationally develop new therapies. This paper reviews the mechanisms, background and progress of small molecule CDK4 inhibitors in the management of melanoma.

Keywords: CDK inhibitors; CDK4; CDKN2A; cyclin D; cyclin-dependent kinases; melanoma; p16.

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Conflict of interest statement

Financial & competing interests disclosure GA McArthur receives research grant support from Pfizer, Celgene and Ventana. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Regulation of the cell cycle and cyclin-dependent kinase inhibitors in development.
See this image and copyright information in PMC

References

    1. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann. Oncol. 2007;18(3):581–592. - PubMed
    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J. Clin. 2013;63(1):11–30. - PubMed
    1. https://clinicaltrials.gov Clinical trials database: NCT01820364.
    1. Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N. Engl. J. Med. 2005;353(20):2135–2147. - PubMed
    1. Walker GJ, Flores JF, Glendening JM, Lin AH, Markl ID, Fountain JW. Virtually 100% of melanoma cell lines harbor alterations at the DNA level within CDKN2A, CDKN2B, or one of their downstream targets. Genes Chromosomes Cancer. 1998;22(2):157–163. - PubMed

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