DNA crosslinking and DNA damage pathway via platinum-DNA adducts (null)

This entry describes the biological pathway and mechanism of action of platinum-based chemotherapeutics, particularly carboplatin. It involves the direct chemical modification of genomic DNA through the formation of platinum-DNA adducts, leading to interstrand and intrastrand crosslinks. These DNA lesions inhibit DNA replication and transcription, induce cell cycle arrest, and ultimately trigger apoptosis or necrosis in tumor cells. While effective in cancer treatment, it is a broad process rather than a specific single molecular target like a protein or receptor.

Other names

Platinum-DNA adduct formationDNA platinationDNA interstrand crosslink formationcarboplatin-induced DNA damage pathway

Formation of monoadducts and diadducts on DNA: Carboplatin forms covalent bonds with purine bases at the N7 position. - Interstrand and intrastrand crosslinks: These lesions inhibit DNA replication and transcription. - Induction of apoptosis/necrosis: The resulting cellular stress triggers programmed cell death or necrosis in tumor cells. - Inhibition of repair mechanisms: Resistance can arise from enhanced repair pathways such as nucleotide excision repair (NER) or mismatch repair