RT Journal Article
SR Electronic
T1 Identification of Genes That Mediate Sensitivity to Cisplatin
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1153
OP 1160
DO 10.1124/mol.60.6.1153
VO 60
IS 6
A1 H. Niedner
A1 R. Christen
A1 X. Lin
A1 A. Kondo
A1 S. B. Howell
YR 2001
UL http://molpharm.aspetjournals.org/content/60/6/1153.abstract
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.