CDK4 inhibitors an emerging strategy for the treatment of melanoma

Belinda Lee; Grant A McArthur

doi:10.2217/mmt.15.14

CDK4 inhibitors an emerging strategy for the treatment of melanoma

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

Authors

Belinda Lee^{1

1}, Grant A McArthur^{1

2

3

4

5

1

2

3

4

5}

Affiliations

¹ Department of Cancer Medicine, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Australia.
² Department of Pathology, University of Melbourne, Parkville, Australia.
³ Department of Medicine, St Vincent's Hospital, University of Melbourne, Victoria St, Fitzroy, Australia.
⁴ Sir Peter MacCallum Department of Oncology, University of Melbourne, St Andrews Place, East Melbourne, Australia.
⁵ Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne VIC 8006, Australia.

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 p16^INK4A-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.

Publication types

Review