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

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. Inhibitio...

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Bibliographic Details
Published in:Clinical cancer research 2010-09, Vol.16 (18), p.4503-4508
Main Authors: MONTAGNOLI, Alessia, MOLL, Jürgen, COLOTTA, Francesco
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apoptosis - drug effects
Apoptosis - genetics
Apoptosis - physiology
Biological and medical sciences
Cell Cycle Proteins - antagonists & inhibitors
Cell Cycle Proteins - genetics
Cell Cycle Proteins - physiology
Clinical Trials, Phase I as Topic
DNA Replication - drug effects
DNA Replication - genetics
Humans
Medical sciences
Models, Biological
Molecular Targeted Therapy - methods
Molecular Targeted Therapy - trends
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - metabolism
Pharmacology. Drug treatments
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - physiology
Therapies, Investigational - methods
Therapies, Investigational - trends
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Summary: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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.ccr-10-0185