Targeting molecular signals in chk1 pathways as a new approach for overcoming drug resistance.
The common clinical problem in the successful treatment of cancer is the resistance of cancer cells to chemotherapeutic drugs. Chemotherapy kills drug-sensitive cells, but leaves behind a higher proportion of drug-resistant cells. The resistance can be due to altered drug accumulation, retention, metabolism and distribution, or to reduced drug-target interaction. More recently, cell cycle progression, DNA mismatch repair (MMR) and cell death have been shown to play an important role in the regulation of cell resistance to anticancer drugs. Chkl regulation pathways, DNA MMR and p73, as well as altered apoptotic cell death involved in the cell resistance toward DNA damaging agents will be reviewed in this article.
Hapke
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Department of Pharmacology and Therapeutics, Grace Cancer Drug Center Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Yin
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Rustum
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D000071877:Checkpoint Kinase 1; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1