Platinum Drugs

Platinum Drugs Mechanism of Action
Carboplatin, cisplatin, oxaliplatin Damages DNA by forming intra-strand crosslinks or platinum adducts that lead to cell death
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  1. Platinum-induced DNA damage is primarily repaired by the process of nucleotide excision mediated by a complex of enzymes and proteins including ERCC1. During this repair process, double strand breaks (DSB) in DNA are generated, which must also be repaired. The most faithful DSB repair mechanism is by the homologous recombination DNA repair pathway, which requires the activity of the BRCA1 protein.
  2. DNA damage response leads to activation of p53 and other molecules which cause growth arrest or cell death by apoptosis, including p21, a cell cycle inhibitor.
  3. Anti-apoptotic proteins bcl2 and bcl-xl block apoptotic cell death.
  4. MT acts as a cellular sink for platinum drugs.

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Green squares, sensitivity markers. Red squares, resistance markers