DNA crosslink (platinum-induced)

Platinum-based compounds, such as cisplatin, carboplatin, and oxaliplatin, exert their antitumor effects by forming covalent **DNA crosslinks**, predominantly intrastrand links between adjacent guanine bases at the N7 position via platinum–DNA adducts[2][4][5]. These **crosslinks disrupt the DNA double helix**, interfering with DNA replication and transcription by preventing strand separation, and can also impede DNA–protein interactions, including the formation of DNA–protein cross-links[1][5]. At high levels, the accumulation of these lesions overwhelms the DNA repair machinery (notably nucleotide excision repair and homologous recombination), ultimately triggering apoptosis or cell cycle arrest in rapidly dividing tumor cells[2][3][5][6]. The clinical use of platinum agents is widespread in oncology, deriving cytotoxicity principally from these DNA crosslinking events, which are not receptor-mediated but are instead **chemical modifications of the DNA itself**, making the DNA crosslink a **pharmacological lesion rather than a molecular entity or canonical receptor**[4][5]. While DNA crosslinking is the intended therapeutic mechanism, it is not a logical drug "target" in the sense of a single gene, receptor, or protein, but rather a macromolecular lesion produced by therapeutic intervention. **Note:** "DNA crosslinking via platinum-based compound" is not a distinct gene, protein, or receptor, but describes a **type of DNA damage lesion** induced pharmacologically. There is no stable, singular biological entity with this name—rather, it encompasses a class of chemical lesions resulting from platinum compound activity. This makes the entry **incorrect as a canonical therapeutic target** (is_incorrect: true).

Other names

Platinum–DNA adductDNA–platinum crosslinkDNA–protein cross-link (for specific lesions including proteins)Platinum-induced DNA adduct

Formation of DNA adducts that cause intrastrand and interstrand DNA crosslinks, disrupting DNA structure and function[2][4][5] - Inhibition of DNA replication and transcription, leading to DNA damage and cell death[2][4][5] - Induction of apoptosis via failed DNA repair and signaling cascades[2][4][6]