Cellular DNA (targeted via platinum-DNA adduct formation and cross-linking) (null)

Platinum-based anticancer drugs, such as cisplatin, exert their cytotoxicity primarily by targeting cellular DNA to form platinum-DNA adducts and cross-links, principally at the N7 position of guanine residues. These lesions include intrastrand and interstrand crosslinks, as well as DNA-protein cross-links, which disrupt DNA replication and transcription, activate the DNA damage response, and can ultimately induce apoptosis. DNA is not a conventional drug target (like a receptor or enzyme) but acts as the substrate for platinum-induced modifications that underpin the pharmacological and toxic effects of these agents. The degree and type of DNA adducts formed, as well as cellular repair efficiency, influence therapeutic efficacy and resistance to platinum-based chemotherapy.

Other names

DNA (when referenced as the direct target in platinum chemotherapy)Pt-DNA adductsPlatinum-DNA cross-linksPlatinum-induced DNA lesions

Formation of platinum-DNA adducts (covalent binding mainly at guanine N7) Induction of intrastrand and interstrand DNA cross-links Stalling of DNA replication and transcription Activation of DNA damage response pathways (notably nucleotide excision repair) Triggering apoptotic cell death if damage is irreparable