Identification of genes that mediate sensitivity to cisplatin.
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.
Niedner
H
H
Department of Medicine and the Cancer Center, University of California, San Diego, La Jolla, California 92093-0058, USA.
Christen
R
R
Lin
X
X
Kondo
A
A
Howell
S B
SB
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018736:DNA Adducts; D011088:DNA Ligases / Q000235:genetics*; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D018736:DNA Adducts; D016159:Tumor Suppressor Protein p53; D017868:Cyclic AMP-Dependent Protein Kinases; D004255:Deoxyribodipyrimidine Photo-Lyase; D011088:DNA Ligases; D002945:Cisplatin