Cisplatin mechanism of action

Cisplatin binds directly to DNA, inhibiting synthesis by altering the DNA template via formation of intra-strand and inter-strand cross links. These cross-links are generated by an aquated complex that acts as a bifunctional alkylating agent. Cytotoxic effects of cisplatin are cell-cycle independent, and synergy between cisplatin and antimetabolites has been demonstrated both in vitro and in clinical trials. The mechanism behind this synergy has not been fully explained; the most commonly held hypothesis is that this is due to a malfunction in DNA repair processing.

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