Doctors may be able to treat cancer effectively by combining arsenic with other therapies, according to a study published in the Proceedings of the National Academy of Sciences (2010 Jul 12. [Epub ahead of print]).
In a study led by Jynho Kim, DVM, PhD, a postdoctoral scholar at Stanford University School of Medicine, researchers examined a two-pronged approach to treating cancer caused by a malfunction in the Hedgehog pathway, a critical cellular signaling cascade. The authors explained that the mechanism of action studied in their experiments differs from what happens during arsenic poisoning, which occurs when higher levels of the compound stop energy production within a cell.
When Philip Beachy, PhD, professor of developmental biology and the Ernest and Amelia Gallo Professor in the School of Medicine, and colleagues studied the effect of arsenic trioxide in cultured human and mouse cells and in laboratory mice with brain tumors, they found that relatively low levels of the compound block one of the final steps of the Hedgehog pathway. As a result, the expression of a select few of the cell’s genes is prevented and since only the end of the pathway is affected, the cancer cell has fewer opportunities to mutate and sidestep arsenic’s inhibitory effect.
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In another study, researchers studied mice with a type of brain tumor known to be dependent on Hedgehog signaling and found that treating the mice with arsenic trioxide slowed or stopped tumor growth. In addition, researchers reported 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,” concluded Dr. Beachy.
