We are analyzing https://link.springer.com/article/10.1007/s10555-007-9045-3.

Title:
The roles of copper transporters in cisplatin resistance | Cancer and Metastasis Reviews
Description:
Platinum-based antitumor agents have been effective in the treatments of many human malignancies but the ultimate success of these agents is often compromised by development of drug resistance. One mechanism associated with resistance to platinum drugs is reduced intracellular accumulation owing to impaired drug intake, enhanced outward transport, or both. Mechanisms for transporting platinum drugs were not known until recent demonstrations that import and export transporters involved in maintenance copper homeostasis are also involved in the transport of these drugs. Ctr1, the major copper influx transporter, has been convincingly demonstrated to transport cisplatin and its analogues, carboplatin, and oxaliplatin. Evidence also suggests that the two copper efflux transporters ATP7A and ATP7B regulate the efflux of cisplatin. These observations are intriguing, because conventional thinking of the inorganic physiologic chemistry of cisplatin and copper is quite different. Hence, understanding the underlying mechanistic aspects of these transporters is critically important. While the mechanisms by which hCtr1, ATP7A and ATP7B transport copper ions have been studied extensively, very little is known about the mechanisms by which these transporters shuffle platinum-based antitumor agents. This review discusses the identification of copper transporters as platinum drug transporters, the structural-functional and mechanistic aspects of these transporters, the mechanisms that regulate their expression, and future research directions that may eventually lead to improved efficacy of platinum-based-based drugs in cancer chemotherapy through modulation of their transporters’ activities.
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Keywords {🔍}

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Topics {✒️}

month download article/chapter platinum-based antitumor agents copper-regulated transporter required cisplatin-resistant cell lines platinum-based-based drugs copper-thiolate polynuclear cluster metal-responsive transcription factor copper-dependent transcriptional activator im-sook song cu-dependent transcription factors copper-induced intramolecular inteaction fluorophore-labeled platinum complexes platinum drug-based treatment extracellular methionine-rich clusters pump/multidrug resistance protein copper transport protein menkes/wilson disease proteins macus tien kuo increased platinum-dna resistance metal ion receptions cisplatin-resistant cancer cells human copper transporter copper-transporting atpase intracellular copper transport regulate copper-stimulated endocytosis copper transporter ctr1 copper transporter atp7a zinc-sensing mechanism cu-transporting atpase ace1 transcription factor human gastric carcinoma platinum drug transporters enhanced outward transport binding transcription factor-1 atp-dependent efflux privacy choices/manage cookies human leukemia cells ovarian cancer patients mediates protein import copper transporters regulate ovarian cancer cells human copper transporter1 transcription factor mac1 transporting platinum drugs protein-binding domains methionine-rich clusters protein-protein interactions metal response element full article pdf copper uptake mediated

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         description:Platinum-based antitumor agents have been effective in the treatments of many human malignancies but the ultimate success of these agents is often compromised by development of drug resistance. One mechanism associated with resistance to platinum drugs is reduced intracellular accumulation owing to impaired drug intake, enhanced outward transport, or both. Mechanisms for transporting platinum drugs were not known until recent demonstrations that import and export transporters involved in maintenance copper homeostasis are also involved in the transport of these drugs. Ctr1, the major copper influx transporter, has been convincingly demonstrated to transport cisplatin and its analogues, carboplatin, and oxaliplatin. Evidence also suggests that the two copper efflux transporters ATP7A and ATP7B regulate the efflux of cisplatin. These observations are intriguing, because conventional thinking of the inorganic physiologic chemistry of cisplatin and copper is quite different. Hence, understanding the underlying mechanistic aspects of these transporters is critically important. While the mechanisms by which hCtr1, ATP7A and ATP7B transport copper ions have been studied extensively, very little is known about the mechanisms by which these transporters shuffle platinum-based antitumor agents. This review discusses the identification of copper transporters as platinum drug transporters, the structural-functional and mechanistic aspects of these transporters, the mechanisms that regulate their expression, and future research directions that may eventually lead to improved efficacy of platinum-based-based drugs in cancer chemotherapy through modulation of their transporters’ activities.
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