Platinum-based antineoplastic
Platinum-based antineoplastic drugs are chemotherapy-agents to treat cancer. They are coordination complexes of platinum.
The main dose-limiting side effect of cancer treatment with platinum compounds is peripheral neurotoxicity.[1]
Mechanism of action [edit]
As studied mainly on cisplatin, but presumably for other members as well, platium-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.
Platium-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 [edit]
- 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
References [edit]
- ^ Donzelli, E.; Carfì, M.; Miloso, M.; Strada, A.; Galbiati, S.; Bayssas, M.; Griffon-Etienne, G.; Cavaletti, G. et al. (2004). "Neurotoxicity of platinum compounds: Comparison of the effects of cisplatin and oxaliplatin on the human neuroblastoma cell line SH-SY5Y". Journal of neuro-oncology 67 (1–2): 65–73. PMID 15072449.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b c d e Kelland, L. (2007). "The resurgence of platinum-based cancer chemotherapy". Nature Reviews Cancer 7 (8): 573–584. doi:10.1038/nrc2167. PMID 17625587.
- ^ 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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