The findings, presented today at the annual meeting of the American Association for Cancer Research, focus on melanoma — a cancer that is difficult to treat, especially in its later stages. The prognosis is generally worse for patients whose tumors have high levels of NO, says Luiz Godoy, an MIT research associate and lead author of the study. Godoy and his colleagues have unraveled the mechanism behind melanoma’s resistance to cisplatin, a commonly used chemotherapy drug, and, in ongoing studies, have found that cisplatin treatment also increases NO levels in breast and colon cancers.
“Now we have a mechanistic link between nitric oxide and the increased aggressiveness of melanoma,” says Douglas Thomas, an assistant professor of medicinal chemistry and pharmacognosy at the University of Illinois at Chicago, who was not part of the research team. “It certainly would be worth exploring whether this mechanism is also present in different tumor types as well.”
The MIT researchers also found in some cancer cells, NO levels were five times higher than normal following cisplatin treatment. Godoy is now investigating how cisplatin stimulates that NO boost, and is also looking for other proteins that NO may be targeting.
Researchers in Wogan’s lab also plan to start testing cisplatin in combination with drugs that block NO production in animals.
The research was funded by the National Cancer Institute and the National Institute of Environmental Health Sciences. The research team also published its findings in a November 2012 article in the Proceedings of the National Academy of Sciences. Other authors of that paper were graduate student Chase Anderson, postdoc Rajdeep Chowdhury and technical associate Laura Trudel.
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