Arsenic could be a potential cancer treatment

WASHINGTON - A form of arsenic-the notorious poison-could be useful in treating a variety of cancers, according to a study by researchers at the Stanford University School of Medicine.

Arsenic trioxide has been used as a therapy for a particular type of leukemia for more than 10 years.

Combining arsenic with other therapies may give doctors a two-pronged approach to beating back forms of the disease caused by a malfunction in a critical cellular signaling cascade called the Hedgehog pathway.

The U.S. Food and Drug Administration has already approved arsenic trioxide for use in humans, which could pave the way for clinical trials of this approach.

“Many pharmaceutical companies are developing anticancer drugs to inhibit the Hedgehog pathway,” said Dr. Philip Beachy, senior author of the study.

In addition, Beachy recently identified an antifungal drug commonly used in humans, itraconazole, as a Hedgehog pathway inhibitor.

“However, these compounds target a component of the pathway that can be mutated with patients then becoming resistant to the therapy. Arsenic blocks a different step of the cascade,” he said.

The researchers studied the effect of arsenic trioxide in cultured human and mouse cells and in laboratory mice with a brain tumour known as medulloblastoma.

They found that relatively low levels of the compound, equivalent to those approved for use in treating patients with acute promyelocytic leukaemia, block one of the last steps of the Hedgehog pathway; it prevents the expression of a select few of the cell’s genes in response to external messages.

Because only the tail end of the pathway is affected, a cancer cell has fewer opportunities to mutate and sidestep arsenic’s inhibitory effect.

On the other hand, another Hedgehog pathway inhibitor called cyclopamine acts near the beginning of the signalling cascade.

The researchers studied human cells in culture and discovered that levels of arsenic trioxide similar to those currently used in patients with acute promyelocytic leukemia inhibit the Hedgehog pathway.

Specifically, the researchers found that arsenic trioxide blocks the ability of a protein called Gli2 to induce gene transcription in the nucleus.

Treating mice with arsenic trioxide slowed or stopped tumor growth.

They also found that combining arsenic trioxide with cyclopamine was even more effective in blocking the pathway in cultured cells.

“Arsenic might be especially effective for treating some types of cancers in combination with other drugs that act at different levels of the Hedgehog pathway, such as the cyclopamine mimics that pharmaceutical companies are developing, or itraconazole, an approved drug that we have recently shown also acts at the level of Smoothened,” said Beachy.

The study is published online in the Proceedings of the National Academy of Sciences. (ANI)