DNA (via formation of platinum-DNA adducts)

The canonical molecular target of platinum-based anticancer drugs is **cellular DNA**; these agents, such as cisplatin, carboplatin, and oxaliplatin, act primarily by forming **platinum-DNA adducts**, including intra- and inter-strand DNA cross-links and monofunctional adducts[5][2][1]. The platinum atom binds covalently to nucleophilic sites on DNA, mainly the N7 position of purines, causing conformational distortions that stall replication and transcription, activate DNA damage response pathways, and frequently result in cell cycle arrest and apoptosis if the lesions are not repaired[8][6][2][5]. Platinum-DNA adducts are cytotoxic because they are recognized as DNA damage, leading to robust anti-tumor effects[3][5]. However, the formation and persistence of these adducts is determined by DNA repair mechanisms, predominantly nucleotide excision repair (NER)[4][5]. The levels of platinum-DNA adducts and expression of repair factors such as ERCC1 can serve as biomarkers for chemotherapy efficacy and resistance[4][7]. Safety concerns arise from similar effects in non-cancerous cells, contributing to well-known side effects associated with platinum-based drugs[5].

Other names

DNA–platinum adductPlatinum-DNA cross-linkCisplatin–DNA adductDNA as platinum drug target

Direct covalent binding of platinum to DNA bases, mainly at guanine N7 positions, forming intra- and inter-strand DNA cross-links and monofunctional adducts[5][2]. Induction of bulky lesions that stall DNA replication and transcription, triggering DNA damage response pathways and, if unrepaired, apoptosis[6][8][2][5].