07 Dec Cancer-fighting agent heads for clinical trials
Wauwatosa, Wis. – Now that Christopher Chitambar, a physician researcher at the Medical College of Wisconsin Cancer Center, has found that a gallium compound might be an effective anti-tumor agent, it’s time for the test.
If the compound is found to be safe and effective in forthcoming clinical trials, it could treat forms of non-Hodgkin’s lymphoma that are resistant to certain therapies. Non-Hodgkin’s lymphoma is a cancer of the human lymphatic system, which is comprised of blood-filtering tissues that help fight infection and disease.
Clinical trials will begin in the near future to see if the compound, gallium maltolate, is a viable alternative to gallium nitrate therapy. Gallium maltolate was invented and patented by Lawrence R. Bernstein, Ph.D, of Menlo Park, Calif., who also discovered it as a way to treat lymphoma. Bernstein introduced the compound to Chitambar and has encouraged him to incorporate it into his own lymphoma studies.
According to the Medical College, the incidence of non-Hodgkin’s lymphoma in the United States has almost doubled since the 1970s. It is estimated that there now are 360,000 Americans living with the disease, and more than 58,000 new cases are diagnosed annually. Despite advances in therapy, the mortality from non-Hodgkin’s lymphoma remains high.
Chitambar said a “substantial percentage of lymphoma patients have not responded to gallium nitrate therapy,” and his research indicates that gallium maltolate is an effective anti-tumor agent for inhibiting the growth of human lymphoma cells that are resistant to gallium nitrate.
Metal detector
Chitambar’s research focuses on the role of iron and other metals in DNA synthesis and the growth of malignant cells. It also concentrates on unraveling cellular processes involved in tumor cell death and tumor cell resistance to metal-based drugs.
He has attempted to develop strategies to address iron-dependent malignant cell growth and to improve the efficacy of cancer chemotherapy by interrupting the flow of iron and other metals within cells.
At the moment, the cellular basis for tumor cell resistance to gallium nitrate is not well understood, but Chitambar’s research has found gallium maltolate to be a unique formulation that bypasses the cellular pathways involved in gallium resistance. It is able to deliver gallium to molecules within the cell that are involved in inducing cell death.
Gallium complexes are among the therapeutic strategies being evaluated for limiting tumor growth. Since Chitambar’s gallium studies began in 1984, he has discovered that gallium nitrate inhibits tumor cell growth by blocking a key enzyme that is vital for DNA synthesis. He also discovered that when gallium nitrate was combined with hydroxyurea, a drug known to inhibit the same enzyme, its anti-cancer activity was enhanced.
His work led to a clinical trial at Froedtert Hospital in which the drug was combined with gallium nitrate to treat patients with advanced relapsed non-Hodgkin’s lymphoma, and it was effective in approximately 40 percent of the patients.
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