Arsenic has long been famous as a poison, but researchers now think it may be able to help some people.
Scientists from the Cancer Center at Beth Israel Deaconess Medical Center in Boston examined whether arsenic could be combined with an existing cancer drug to help treat the disease. Their study, published in Nature Communications on Thursday, raises the hope of new treatment strategies for several cancers.
Arsenic, which is naturally occurring, has long been used as a medicine. According to Dartmouth University's Toxic Metals Superfund Research Program, it was the first effective treatment for syphilis and was also used to treat bacterial and parasitic infections before the invention of antibiotics.
When the scientists combined arsenic trioxide, a type of arsenic approved by the U.S. Food and Drug Administration, with trans-retinoic acid, the treatment was very effective against acute promyelocytic leukemia, they said. The mechanism by which they work together raises the prospect of further treatments.
The drugs act against Pin1, an enzyme in the body that when inhibited, could treat cancer. Pin1 activates more than 40 proteins that can drive cancer, and deactivates 20 proteins that suppress tumors.
The new treatment was able to inhibit multiple cancer-driving pathways as well as eliminate cancer stem cells in both cell and animal tests, as the arsenic binds, inhibits, and degrades Pin1, and helps enhance the effects of the trans-retinoic acid.
The combination also worked against tumors derived from patients with triple-negative breast cancer, which has the lowest survival rate of all breast cancers.
"Our discovery strongly suggests an exciting new possibility of adding arsenic trioxide to existing therapies in treating triple-negative breast cancer and many other cancer types, especially when patients' cancers are found to be Pin1-positive," Xiao Zhen Zhou, a leader of the study, said in a press release. "This might significantly improve the outcomes of cancer treatment."
In tests on mice, those whose Pin1 enzyme was limited were highly resistant to developing cancers, and didn't show any obvious defects over half their lifespan.
"It's gratifying to see this combination of all-trans retinoic acid and arsenic trioxide that my lab discovered to be curative in the treatment of acute promyelocytic leukemia translate into possible approaches for the treatment of other cancers," Pier Paolo Pandolfi, director of the Cancer Center and Cancer Research Institute at the hospital, said in a press release. "Indeed, it is interesting to speculate that this combination may even prove curative in other tumor types yet to be discovered."
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