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Digoxin has a long history as a treatment for heart failure.
New testing paradigm combined epidemiological and laboratory testing.
Repositioning existing therapies could speed drug approval time.
ORLANDO, Fla. – Scientists have identified digoxin as a possible therapy for prostate cancer, using a combination of laboratory science and epidemiology that is unprecedented in its cooperative nature.
“Epidemiologists and basic scientists often do not understand each other, as we often are only clear on our own strengths and the others weaknesses,” said Elizabeth Platz, Sc.D., M.P.H, professor of epidemiology and the Martin D. Abeloff, M.D., scholar in cancer prevention at Johns Hopkins University.
For the current paper, published in Cancer Discovery, the newest journal of the American Association for Cancer Research, which will debut at the AACR 102nd Annual Meeting 2011, Platz shares authorship with Srinivasan Yegnasubramanian, M.D., Ph.D., assistant professor of oncology at Johns Hopkins. Platz said the multidisciplinary team of scientists had come together to identify existing drugs that could be used to treat prostate cancer in a process called drug repositioning.
“If you use drugs that are already available then you have a long history of safety research that does not necessarily need to be redone, and we can move more quickly to testing whether the drug will actually work in a new setting,” said Platz.
The idea of drug repositioning has been offered before, but each branch of scientific inquiry had enough flaws that it had not previously gained substantial traction. “When we combined the basic science and the epidemiology approaches, the flaws were not the same and were covered by their respective strengths,” she said.
Platz, Yegnasubramanian and colleagues from Johns Hopkins and Harvard combined a high-throughput laboratory-based screen and a large, prospective cohort study.
In the first stage, the laboratory scientists conducted an in vitro prostate cancer cell toxicity screen of 3,187 compounds, and digoxin, a known heart failure drug emerged as a leading candidate due to its potency in inhibiting cell proliferation in vitro.
In the second stage, the epidemiology team observed the drugs use in a cohort of 47,884 men who were followed from 1986 to 2006. Regular digoxin users had a 24 percent lower risk of prostate cancer, while those who had used the drug for more than 10 years had a 46 percent reduced risk.
Platz said this multidisciplinary team is now working toward identifying the pathways digoxin targets in prostate cancer. Knowing the targets will help inform the design of a trial that will confirm whether digoxin or molecules acting on the same targets has utility as a prostate cancer treatment.
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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the worlds oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. Including Cancer Discovery, the AACR publishes seven major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. AACR journals represented 20 percent of the market share of total citations in 2009. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists.
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