Abstract
The DNA damage response includes not only checkpoint and apoptosis, but also direct activation of DNA repair networks. Downstream in the DNA damage response pathway are Chk1, an essential checkpoint kinase, and Chk2, which plays a critical role in p53-dependent apoptosis. Chk1 inhibition is expected to lead to chemosensitization of tumors, while Chk2 inhibition could protect normal sensitive tissues from some chemotherapeutic agents. Drugs targeting Chk1 and Chk2 have the potential to significantly improve the therapeutic window of DNA damaging agents available in the clinic.
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Checkpoint Kinase 1
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Checkpoint Kinase 2
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DNA Damage / drug effects*
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DNA Damage / genetics
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Drug Design*
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / genetics
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Genes, cdc / drug effects*
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Genes, cdc / physiology
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Humans
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Neoplasms / drug therapy
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Neoplasms / genetics
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Neoplasms / metabolism
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Protein Kinase Inhibitors*
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases*
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Protein Kinases
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Checkpoint Kinase 2
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CHEK1 protein, human
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CHEK2 protein, human
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Checkpoint Kinase 1
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Protein Serine-Threonine Kinases