Cell Cycle Regulation and 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.
Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
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Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia. grant.mcarthur@petermac.org.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia. grant.mcarthur@petermac.org.|Molecular Oncology Laboratory, Oncogenic Signalling and Growth Control Program, East Melbourne, Australia. grant.mcarthur@petermac.org.|Translational Research Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. grant.mcarthur@petermac.org.|Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Australia. grant.mcarthur@petermac.org.|Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, VIC, 8006, Australia. grant.mcarthur@petermac.org.
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D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D051358:Cyclin-Dependent Kinase 4
Anti-mitotic agents; CDK4/6 inhibitors; Cell cycle regulation; Chk1; G1-S checkpoint; G2-M checkpoint; MK2; Metastatic melanoma; WEE1