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DNA (carboplatin adduct site)

Molecular classification
Other (drug–DNA covalent adduct)
01

Overview

Carboplatin is a platinum-based chemotherapeutic agent whose cytotoxic effect is primarily mediated by formation of covalent adducts with DNA, especially at the N7 positions of purine bases (guanine and adenine). These carboplatin–DNA adducts cause intra- and interstrand crosslinks, leading to inhibition of DNA replication and transcription, triggering cellular apoptosis and death. The rate of adduct formation is slower than cisplatin, resulting in lower potency but fewer side effects. The extent and repair of these adducts determine sensitivity and resistance in cancer therapy. Carboplatin–DNA adduct formation plays a critical biological role in the drug's anticancer mechanism but is a product of the drug–biomolecule interaction, not a conventional protein or receptor drug target. Key point: This entry is not a proper therapeutic target (such as a receptor or enzyme), but a drug-induced DNA lesion. For ontology or structured data, use “DNA (carboplatin binding site)” or “DNA (platinum adduct site)” as the canonical target.

Other names
Carboplatin–DNA adductsPlatinum–DNA adductsDNA–carboplatin complexesPlatinum adducted DNA
02

Mechanism of action

Formation of platinum–DNA adducts leading to DNA crosslinking. Blocks DNA replication and transcription, causes mutations, induces apoptosis.

03

Biological functions

Inhibition of DNA replicationInhibition of DNA transcriptionInduction of DNA damageInduction of apoptosisInduction of cell death
04

Disease associations

Cancer
05

Safety considerations

Myelosuppression (especially neutropenia and thrombocytopenia)Resistance via enhanced DNA repairReduced formation of adducts may lead to reduced efficacyTumor/cellular resistance mechanisms involve increased detoxification and repair
06

Interacting drugs

Carboplatin

3 more in the full profile.

07

Biomarkers

ERCC1 (excision repair cross-complementation group 1)RRM1 (ribonucleotide reductase M1)Levels of carboplatin–DNA adducts (pharmacodynamic marker)

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