Clinical aspects of cell death in breast cancer: the polyamine pathway as a new target for treatment.
Because intracellular polyamines have a critical role in cell proliferation and death pathways, the polyamine metabolic pathway represents a potential target for intervention in cancers. A number of polyamine analogues have been identified that downregulate polyamine synthesis and enhance polyamine catabolism, thereby depleting intracellular polyamines. Treatment of human breast cancer cell lines in culture with these analogues has been shown to decrease cell proliferation and induce programmed cell death. Phase I studies with one analogue are now complete, setting the stage for phase II trials to determine efficacy, in addition to preclinical studies to examine combinations of polyamine analogues and conventional cytotoxics.
Davidson
N E
NE
The Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Hahm
H A
HA
McCloskey
D E
DE
Woster
P M
PM
Casero
R A
RA
D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D017321:Clinical Trials, Phase I as Topic; D004305:Dose-Response Relationship, Drug; D004967:Estrogens; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D011073:Polyamines / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000970:Antineoplastic Agents; D004967:Estrogens; D009363:Neoplasm Proteins; D011073:Polyamines; D013096:Spermine; D000099228:Diamine N-Acetyltransferase; C059685:N(1),N(11)-diethylnorspermine; C083629:N(1)-ethyl-N-(11)-((cyclopropyl)methyl)-4,8-diazaundecane-1,11-diamine