Chelating drugs and
chelator metal complexes are used for the prevention, diagnosis and treatment of
cancer.
Cancer cells and normal cells require essential
metal ions such as
iron,
copper and
zinc for growth and proliferation.
Chelators can target the metabolic pathways of
cancer cells through the control of
proteins involved in the regulation of these metals and also of other molecules involved in cell cycle control, angiogenesis and metastatic suppression. Other targets include the inhibition of specific
proteins such as
ribonucleotide reductase involved in
DNA synthesis, the inhibition of
free radical damage on
DNA caused by
iron and
copper catalytic centers, the inhibition of microbial growth in immuno compromised
cancer patients and the decorporation of radioactive and other toxic metals causing
cancer. Chelating drugs and
metal ions can affect the metabolism, efficacy and toxicity of anti-
cancer drugs such as
doxorubicin,
mitozantrone, bleiomycin and
hydroxyurea (HU). Although many experimental
chelators have been shown to be effective as anti-
cancer agents, only a few, e.g.,
dexrazoxane,
deferoxamine (DFO) and
triapine, have reached the stage of clinical testing or application. In many experimental models,
deferiprone (L1) has been shown to be effective in
cancer prevention and treatment, and in the inhibition of
doxorubicin-induced
cardiotoxicity. New anti-
cancer drugs could be developed using
chelators and
chelator complexes with
platinum and other metals, and also new protocols of combinations of
chelators with known anti-
cancer drugs.