期刊
CURRENT OPINION IN ONCOLOGY
卷 27, 期 2, 页码 141-150出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCO.0000000000000159
关键词
CDK; cell cycle control; MDM2; melanoma; p53
类别
资金
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
Purpose of review This review highlights recent clinical developments in the therapeutic targeting of cell cycle control in melanoma with cyclin-dependent kinase inhibitors, checkpoint kinases, MDM2, MDM4 and p53 inhibitors. Recent findings The high prevalence of activating genetic aberrations along the p16(INK4A):cyclinD-CDK4/6:RB pathway in melanoma and increasing evidence that alterations in this pathway are linked to melanomagenesis, make targeting the p(16INK4A):cyclinD-CDK4/6: RB pathway in melanoma logical and highly attractive. The presence of elevated CDK4 activity appears to correlate with greater CDK4/6 inhibitor therapeutic activity, whereas the loss of RB1 has been linked to CDK inhibitor resistance. Other novel compounds targeting cell cycle control via reactivating wild-type p53 and checkpoint kinases are also currently under investigation in melanoma. Summary Cell cycle control is a promising target in the management of melanoma with early data reporting therapeutic benefit with cyclin-dependent kinase inhibitors, MDM2, and p53 reactivation compounds. Many of these drugs have entered phase I and II clinical trial development. Preliminary data from these studies are discussed in this review along with future treatment strategies for maximizing treatment outcomes in advanced melanoma.
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