Gallium compounds as antineoplastic agents.
OBJECTIVE
The purpose of this review is to provide an outline of the basic and clinical information on gallium nitrate as an antineoplastic agent. Although early clinical trials indicated that gallium nitrate had activity against lymphoma and bladder cancer, its subsequent development centered primarily on its effect on bone metabolism and not on its antineoplastic activity. As a result, the drug was approved for the treatment of hypercalcemia of malignancy. However, pharmaceutical production of gallium nitrate ceased during the late 1990s, bringing several gallium-based clinical trials to a halt. Gallium nitrate has recently become commercially available, thus reopening the door for clinical trials evaluating it as an antineoplastic agent.


RESULTS
Multicenter clinical trials have recently been conducted to reevaluate gallium nitrate for the treatment of lymphoma. An oral formulation of gallium is also in development. Gallium's mechanisms of action include its binding to transferrin, targeting to transferrin receptors on lymphoma cells, and inhibiting ribonucleotide reductase. Recent investigations show that gallium activates caspases and induces apoptosis through the mitochondrial pathway, whereas complementary DNA microarray studies suggest that changes in intracellular trafficking pathways may be important in gallium resistance.


CONCLUSIONS
Gallium nitrate has demonstrated activity against lymphoma and bladder cancer, which is likely the result of selective targeting of these malignancies. An important property of gallium nitrate is that it is not myelosuppressive and it lacks cross-resistance to other drugs. Further investigations are needed to understand better its molecular targets and to determine its clinical efficacy in combination with other drugs.
Chitambar
Christopher R
CR
Division of Neoplastic Diseases, Department of Medicine, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI 53226, USA. chitambr@mcw.edu
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005708:Gallium / Q000627:therapeutic use*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D005708:Gallium; C027235:gallium nitrate