Platinum-based antineoplastic

Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents to treat cancer. They are coordination complexes of platinum. These drugs are used to treat almost 50% of cancer patients. In this form of chemotherapy, popular drugs include cisplatin and carboplatin, but several have been proposed or are under development.^[1]

The main dose-limiting side effect of cancer treatment with platinum compounds is neurotoxicity, which causes peripheral neuropathies including polyneuropathy.^[2]

Mechanism of action

As studied mainly on cisplatin, but presumably for other members as well, platinum-based antineoplastic agents cause crosslinking of DNA as monoadduct, interstrand crosslinks, intrastrand crosslinks or DNA protein crosslinks. Mostly they act on the adjacent N-7 position of guanine, forming 1, 2 intrastrand crosslink.^[3]^[4] The resultant crosslinking inhibit DNA repair and/or DNA synthesis in cancer cells.

Platinum-based antineoplastic agents are sometimes described as "alkylating-like" due to similar effects as alkylating antineoplastic agents, although they do not have an alkyl group.^[5]

Examples

Strategies for improving platinum-based anticancer drugs usually involve changes in the neutral spectator ligands, which are usually nitrogenous. Changes in the nature of the anions (halides vs various carboxylates), and changes in the oxidation state of the metal (Pt(II) vs Pt(IV)). Nanotechnology has been explored to deliver platinum more efficiently in the case of Lipoplatin, which is introduced into the tumor sites thereby reducing the chance of toxicity.^[6]

Cisplatin, the first to be developed.^[7] Cisplatin is particularly effective against testicular cancer; the cure rate was improved from 10% to 85%.^[8]