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 other's 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 drug's 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.


Source: AACR