One focus of our laboratory is to investigate the potential clinical use of arsenic. Arsenic provides a very effective treatment for one specific type of leukemia (acute promyelocytic leukemia; APL), although resistance can develop. Our research aims to understand how resistance develops in APL and why other cancer cells are typically more resistant to arsenic. We propose that understanding these mechanisms will permit us to find ways to overcome arsenic resistance and broaden the anticancer activity of arsenic.

Our initial studies showed that the ability of a cell to handle stress may affect its susceptibility to arsenic-induced cell death. We have identified a vitamin E-derivative (trolox) that protects normal cells against stress induced by arsenic, but makes cancer cells more susceptible to the killing effects of arsenic. In animal studies, the combination of trolox with arsenic increases the life-span of mice with tumors, while protecting the liver against arsenic's negative effects.

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