Christopher Chitambar, M.D., a physician researcher at the Medical College of Wisconsin Cancer Center in Milwaukee, has identified a compound that may be effective in treating forms of non-Hodgkin’s lymphoma (a cancer of the lymphatic system) that are resistant to certain therapies. The new agent could also offer the advantages of being administered orally, rather than intravenously, making it more convenient than intravenous agents.
Since the 1970?s, the incidence of non-Hodgkin?s lymphoma in the U.S. has almost doubled, and despite advances in therapy, the mortality from this disease remains high. More than 58,000 new cases are diagnosed annually and it is estimated that there are now 360,000 Americans living with the disease.
Dr. Chitambar?s research revealed that the compound, Titan Pharmaceutical?s gallium maltolate, is an effective anti-tumor agent for inhibiting the growth of human lymphoma cells that are resistant to gallium nitrate. Although the cellular basis for tumor cell resistance to gallium nitrate is not well understood, gallium maltolate appears to be a unique gallium formulation that bypasses the cellular pathways involved in gallium resistance and is able to deliver gallium to molecules within the cell that are involved in inducing cell death.
This pre-clinical, patent-pending therapy is scheduled for clinical trials in the near future. Titan Pharmaceuticals has received an exclusive license from the Medical College of Wisconsin Research Foundation for the use of this intellectual property.
“If proven safe and effective, this agent may offer a viable alternative for a substantial percentage of lymphoma patients whose disease has not responded to gallium nitrate therapy,” says Dr. Chitambar.
Dr. Chitambar?s gallium studies began with basic science research in 1984, leading to his discovery that gallium nitrate inhibits tumor cell growth by blocking an enzyme, ribonucleotide reductase, that is essential for DNA synthesis. He subsequently discovered that when gallium nitrate was combined with hydroxyurea, a chemotherapeutic drug known to inhibit the same enzyme, the anti-cancer activity of gallium nitrate was synergistically boosted.
This preclinical discovery led to a clinical trial at Froedtert Hospital in which gallium nitrate and hydroxyurea were combined to treat patients with advanced relapsed non-Hodgkin?s lymphoma, and proved to be effective in approximately 40 percent of patients with this disease.
Dr. Chitambar?s research, at the MACC (Midwest Athletes Against Childhood Cancer) Fund Research Center, focuses on the role of metals, especially the role of iron, in DNA synthesis and the growth of malignant cells. A major emphasis of his work is to develop strategies to modulate iron-dependent malignant cell growth and to enhance the efficacy of cancer chemotherapy by interrupting the flow of iron and other metals within cells. His research also focuses on unraveling cellular processes involved in tumor cell death and tumor cell resistance to metal-based drugs.
Gallium complexes are among the therapeutic strategies being investigated to inhibit tumor growth. Dr. Chitambar?s research is also leading to a better understanding of iron metabolism in malignant cells and to the development of novel cancer treatment strategies directed at targeting metal-dependent tumor cell growth.