Chelators at the cancer coalface: desferrioxamine to Triapine and beyond.
The importance of iron and copper in cancer biology has been well established. Iron plays a fundamental role in cellular proliferation and copper has been shown to be a significant cofactor for angiogenesis. Early observations with the chelator used for the treatment of iron overload, desferrioxamine, showed that it had promise as an anticancer agent. These results sparked great interest in the possibility of developing more effective iron chelators for cancer therapy. The recent entry into clinical trials of the iron-binding drug, Triapine, provides evidence of the potential of this antitumor strategy. Likewise, chelators originally designed to treat disorders of copper overload, such as penicillamine, trientine, and tetrathiomolybdate, have also emerged as potential anticancer drugs, as they are able to target the key angiogenic cofactor, copper. In this review, we will discuss the development of these and other chelators that show potential as anticancer agents.
Yu
Yu
Y
Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia.
Wong
Jacky
J
Lovejoy
David B
DB
Kalinowski
Danuta S
DS
Richardson
Des R
DR
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D003676:Deferoxamine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D002614:Chelating Agents; D011725:Pyridines; D013882:Thiosemicarbazones; C078157:3-aminopyridine-2-carboxaldehyde thiosemicarbazone; D003676:Deferoxamine