Metal complexes, their cellular targets and potential for cancer therapy.
The development of metal complexes with anticancer activity has had an enormous impact on cancer chemotherapy. The discovery of cisplatin in the 1960's represented a landmark achievement and ushered in a new era in cancer treatment. Despite the fact that cisplatin has achieved significant clinical benefit for several types of solid tumors, its effectiveness has been hampered by toxic side effects and tumor resistance that often leads to the occurrence of secondary malignancies. However, discovery and use of cisplatin have encouraged investigators to search for and develop novel non platinum-containing metal species with superior anti-cancer activity and low side effects. As examples, gallium salts and gold complexes have been evaluated in phase I and phase II trials. Copper-chelating compounds have also shown promising results in both preclinical and clinical studies. This review provides a comprehensive overview of various non platinum metal complexes and metal-chelating compounds and discusses their potential molecular targets in tumor cells and their applications in cancer therapy.
Chen
Di
D
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA.
Milacic
Vesna
V
Frezza
Michael
M
Dou
Q Ping
QP
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D003300:Copper / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery; D005708:Gallium / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D050607:Organogold Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017671:Platinum Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D061988:Proteasome Inhibitors
D000970:Antineoplastic Agents; D050607:Organogold Compounds; D009942:Organometallic Compounds; D017671:Platinum Compounds; D061988:Proteasome Inhibitors; D003300:Copper; D005708:Gallium