Targeting Cell Division Cycle 7 Kinase: A New Approach for Cancer Therapy

被引：93

作者：

Montagnoli, Alessia ^{[1
]}

Moll, Juergen ^{[1
]}

Colotta, Francesco ^{[1
]}

机构：

[1] Nerviano Med Sci Oncol, I-20014 Milan, Italy

来源：

CLINICAL CANCER RESEARCH | 2010年 / 16卷 / 18期

关键词：

HUMAN CDC7-RELATED KINASE; DNA-DAMAGE CHECKPOINT; PROTEIN-KINASE; S-PHASE; REGULATED PROTEIN; REPLICATION; CDC7; INITIATION; COMPLEX; PHOSPHORYLATION;

D O I：

10.1158/1078-0432.CCR-10-0185

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The cell division cycle 7 (Cdc7) is a serine-threonine kinase, originally discovered in budding yeast, required to initiate DNA replication. Human Cdc7 phosphorylates the minichromosome maintenance protein 2 (Mcm2), a component of the DNA replicative helicase needed for genome duplication. Inhibition of Cdc7 in cancer cells impairs progression through S phase, inducing a p53-independent apoptotic cell death, whereas in normal cells, it does not affect cell viability. Small molecule compounds able to interfere with Cdc7 activity have been identified and shown to be effective in controlling tumor growth in animal models. Two Cdc7 inhibitors are currently in phase I clinical development. Inhibition of Cdc7 kinase activity in cancer cells restricts DNA replication and induces apoptotic cell death by an unprecedented molecular mechanism of action. Clin Cancer Res; 16(18); 4503-8. (c) 2010 AACR.

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收藏

页码：4503 / 4508

页数：6

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