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Additionally, patient population characteristics vary between studies, including differences in baseline body mass index, age, gender distribution, and presence of comorbidities such as diabetes

The multifaceted mechanism of action of 5FU involves direct incorporation of its metabolites into DNA (FdUTP) and RNA (FUTP), as well as inhibition of thymidylate synthase (TS) via FdUMP 4,5 , making it more difficult to identify rational combination partners that would enhance clinical responses without eliciting adverse systemic toxicity

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