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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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It is noteworthy that the production of ROS in melanocytes can be amplified under pathological circumstances, exemplified by instances of inflammation and cancer 55