PT - JOURNAL ARTICLE AU - H. Niedner AU - R. Christen AU - X. Lin AU - A. Kondo AU - S. B. Howell TI - Identification of Genes That Mediate Sensitivity to Cisplatin AID - 10.1124/mol.60.6.1153 DP - 2001 Dec 01 TA - Molecular Pharmacology PG - 1153--1160 VI - 60 IP - 6 4099 - http://molpharm.aspetjournals.org/content/60/6/1153.short 4100 - http://molpharm.aspetjournals.org/content/60/6/1153.full SO - Mol Pharmacol2001 Dec 01; 60 AB - Cisplatin (cDDP) is effective against some human tumors, but many are intrinsically resistant and, even among initially sensitive tumors, acquired resistance develops commonly during treatment. It has not been possible to prove which biochemical mechanisms control sensitivity to cDDP. Gene knockout studies in yeast, Dictyostelium discoideum, and mammalian cells have begun to unambiguously identify genes whose products function to modulate the cytotoxicity of cDDP. This review summarizes information currently available about the function of these genes. This comprehensive compilation points to the involvement of regulatory pathways known to mediate apoptosis, cell cycle checkpoint activation, and transcriptional rescue as regulators of cDDP sensitivity. Elucidation of the molecular mechanisms that mediate cDDP resistance holds promise for the design of pharmacological strategies for preventing, overcoming, or reversing this form of drug resistance.