Cisplatin resistance in human cancers.
Cancer chemotherapeutic agents primarily act by damaging cellular DNA directly or indirectly. Tumor cells, in contrast to normal cells, respond to cisplatin with transient gene expression to protect and/or repair their chromosomes. Repeated cisplatin treatments results in a stable resistant cell line with enhanced gene expression but lacking gene amplification for the proteins that will limit cisplatin cytotoxicity. Recently, several new human cell lines have been characterized for cisplatin resistance. These cell lines have led to a better understanding of the molecular and biochemical basis of cisplatin resistance. The c-fos proto-oncogene, a master switch for turning on other genes in response to a wide range of stimuli, has been shown to play an important role in cisplatin resistance both in vitro and in patients. Based on these studies, new strategies have been developed to circumvent and/or exploit clinical cisplatin resistance.
Scanlon
K J
KJ
Department of Medical Oncology, City of Hope Medical Center, Duarte, CA 91010.
Kashani-Sabet
M
M
Tone
T
T
Funato
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D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002945:Cisplatin / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D004351:Drug Resistance; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy; D016761:Oncogene Proteins v-fos / Q000187:drug effects; D000090063:Proto-Oncogene Mas
C000715470:MAS1 protein, human; D016761:Oncogene Proteins v-fos; D000090063:Proto-Oncogene Mas; D002945:Cisplatin