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. 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.
Montagnoli
Alessia
A
Nerviano Medical Sciences Oncology, Nerviano, Milan, Italy. alessia.montagnoli@nervianoms.com
Moll
Jürgen
J
Colotta
Francesco
F
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D017321:Clinical Trials, Phase I as Topic; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D035703:Therapies, Investigational / Q000379:methods* / Q000639:trends
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases