Cell Cycle Regulation and Melanoma

被引：50

作者：

Xu, Wen ^{[1
]}

McArthur, Grant ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Peter MacCallum Canc Ctr, Dept Med Oncol, East Melbourne, Australia

[2] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia

[3] Mol Oncol Lab, Oncogen Signalling & Growth Control Program, East Melbourne, Australia

[4] Peter MacCallum Canc Ctr, Canc Therapeut Program, Translat Res Lab, East Melbourne, Vic, Australia

[5] Univ Melbourne, Peter MacCallum Canc Ctr, East Melbourne, Australia

[6] Peter MacCallum Canc Ctr, Div Res, Locked Bag 1,Beckett St, Melbourne, Vic 8006, Australia

来源：

CURRENT ONCOLOGY REPORTS | 2016年 / 18卷 / 06期

关键词：

Metastatic melanoma; Cell cycle regulation; CDK4/6; inhibitors; G1-S checkpoint; G2-M checkpoint; WEE1; Chk1; MK2; Anti-mitotic agents; DEPENDENT KINASE INHIBITOR; DOSE-ESCALATION TRIAL; ADVANCED SOLID TUMORS; PHASE-I; CANCER-THERAPY; AURORA KINASE; CDK4/6; INHIBITION; ADVANCED MALIGNANCIES; PROMISING TARGET; PURINE ANALOGS;

D O I：

10.1007/s11912-016-0524-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：12

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