Platinum-based antineoplastic

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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[edit]

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[edit]

References[edit]

  1. ^ Donzelli, E.; Carfì, M.; Miloso, M.; Strada, A.; Galbiati, S.; Bayssas, M.; Griffon-Etienne, G.; Cavaletti, G.; Petruccioli, M. G.; Tredici, G. (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. doi:10.1023/B:NEON.0000021787.70029.ce. PMID 15072449.  edit
  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. 
  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. 
  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. 
  5. ^ 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.  edit
  6. ^ Einhorn LH. (1 November 1990). "Treatment of testicular cancer: a new and improved model". J. Clin. Oncol. 8 (11): 1777–81. PMID 1700077.