Platinum-based antineoplastic

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

## Overview

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Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents to treat cancer. They are coordination complexes of platinum.

The main dose-limiting side effect of cancer treatment with platinum compounds is neurotoxicity, which causes peripheral neuropathies including polyneuropathy.[1]

## Mechanism of action

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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.[2][3]

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.[4]

## Examples

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* cisplatin, the first to be developed.[5] Cisplatin is particularly effective against testicular cancer; the cure rate was improved from 10% to 85%.[6]
* carboplatin, a second-generation platinum-based antineoplastic agent[5]
* oxaliplatin[5]
* satraplatin[5]
* picoplatin[5]
* Nedaplatin
* Triplatin
* Lipoplatin, a liposomal version of cisplatin

## References

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1. ↑ PMID 15072449 (PMID 15072449)
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2. ↑ Poklar N, Pilch DS, Lippard SJ, Redding EA, Dunham SU, Breslauer KJ (July 1996). "Influence of cisplatin intrastrand crosslinking on the conformation, thermal stability, and energetics of a 20-mer DNA duplex". Proc. Natl. Acad. Sci. U.S.A. 93 (15): 7606–11. doi:10.1073/pnas.93.15.7606. PMC 38793. PMID 8755522.CS1 maint: Multiple names: authors list (link)
3. ↑ Rudd GN, Hartley JA, Souhami RL (1995). "Persistence of cisplatin-induced DNA interstrand crosslinking in peripheral blood mononuclear cells from elderly and young individuals". Cancer Chemother. Pharmacol. 35 (4): 323–6. doi:10.1007/BF00689452. PMID 7828275.CS1 maint: Multiple names: authors list (link)
4. ↑ Cruet-Hennequart S, Glynn MT, Murillo LS, Coyne S, Carty MP (April 2008). "Enhanced DNA-PK-mediated RPA2 hyperphosphorylation in DNA polymerase eta-deficient human cells treated with cisplatin and oxaliplatin". DNA Repair (Amst.). 7 (4): 582–96. doi:10.1016/j.dnarep.2007.12.012. PMID 18289945.CS1 maint: Multiple names: authors list (link)
5. ↑ 5.0 5.1 5.2 5.3 5.4 Template:Cite doi
6. ↑ Einhorn LH. (1 November 1990). "Treatment of testicular cancer: a new and improved model". J. Clin. Oncol. 8 (11): 1777–81. PMID 1700077.

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