Cancer Biologists Uncover a New Mechanism for an Old Chemo Drug
MIT cancer researchers have discovered surprising mechanism for the long-used chemotherapy drug 5-fluorouracil (5-FU), indicating a potential shift in cancer treatment protocols. Previously believed to work primarily by damaging DNA, this research demonstrates that 5-FU effectively kills colon and gastrointestinal (GI) cancer cells by disrupting RNA synthesis, specifically by damaging ribosomal RNA crucial for protein production.
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Led by MIT’s 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, the study found that the disruption of RNA—particularly ribosomal RNA—is the main mechanism through which 5-FU kills GI cancer cells. Traditionally combined with DNA-damaging drugs, these combinations often proved less effective than expected. Instead, the research suggests that pairing 5-FU with drugs that enhance RNA damage could significantly improve outcomes for GI cancer patients. These insights are expected to pave the way for new clinical trials focused on innovative 5-FU drug combinations and treatment protocols, potentially advancing the standard of care for patients with GI cancers.
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Yaffe, the senior author of the new study, hopes to plan clinical trials for 5-fluorouracil with drugs that would enhance its RNA-damaging effects and kill cancer cells more effectively. Jung-Kuei Chen, a Koch Institute research scientist, and Karl Merrick, a former MIT postdoc, are the lead authors of the paper, published in Cell Reports Medicine.
Category: Pharmaceuticals, Top Story
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