Cell cycle checkpoint proteins and cellular response to treatment by anticancer agents.
The response of cancer cells to treatment with anticancer agents is mediated in part by proteins controlling both the cell cycle progression and the genomic integrity, including p53, p73 and checkpoint proteins chk1 and chk2. We here summarized the cellular functions of these proteins, their alterations in human tumors and the impact of their mutations/alterations on cellular response to treatment, Particular attention has been paid for those studies performed in isogenic cell systems, to minimize as much as possible interference by other alterations invariably present when different cell types are considered. Focus has also be given to the approaches taken to exploit the differential expression of these proteins between normal and tumor cells to improve the selectivity of treatment with anticancer agents.
Damia
Giovanna
G
Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Broggini
Massimo
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D020687:cdc25 Phosphatases / Q000378:metabolism*
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases