Old Chemo Drug Is New Again Because It Can Attack Different Cancers Differently

Since the 1950s a chemotherapy drug known as 5-fluorouracil (5-FU) has been used to treat many types of cancer, including blood cancers and cancers of the digestive tract. Doctors have long believed that the drug works by damaging the building blocks of DNA. However, a new study headed by researchers at MIT has found that in cancers of the colon and other gastrointestinal (GI) cancers 5-FU kills cells by interfering with RNA synthesis.

The findings could have a significant effect on how doctors treat many cancer patients. Usually, 5-fluorouracil is given in combination with chemotherapy drugs that damage DNA, but the new study found that for colon cancer, this combination does not achieve the synergistic effects that were hoped for. Instead, combining 5-FU with drugs that affect RNA synthesis could make it more effective in patients with GI cancers, the researchers say.

“Our work is the most definitive study to date showing that RNA incorporation of the drug, leading to an RNA damage response, is responsible for how the drug works in GI cancers,” said Michael Yaffe, a David H. Koch Professor of Science at MIT, the director of the MIT Center for Precision Cancer Medicine, and a member of MIT’s Koch Institute for Integrative Cancer Research. “Textbooks implicate the DNA effects of the drug as the mechanism in all cancer types, but our data shows that RNA damage is what’s really important for the types of tumors, like GI cancers, where the drug is used clinically.

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