Platinum-based antineoplastic

Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used 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] Addition of platinum-based chemotherapy drugs to chemoradiation in women with early cervical cancer seems to improve survival and reduce risk of recurrence.[2]

The main dose-limiting side effect of cancer treatment with platinum compounds is neurotoxicity, which causes peripheral neuropathies including polyneuropathy.[3]

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 a 1, 2 intrastrand crosslink.[4][5] The resultant crosslinking inhibits 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.[6]

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.[7]

Cisplatin, the first to be developed.[8] Cisplatin is particularly effective against testicular cancer; the cure rate was improved from 10% to 85%.[9]

  1. ^ Johnstone, TC; Park, GY; Lippard, SJ (2014). "Understanding and improving platinum anticancer drugs--phenanthriplatin". Anticancer Res. 34 (1): 471–6. PMC 3937549Freely accessible. PMID 24403503. 

References

  1. ↑
  2. ↑ Falcetta, FS; Medeiros, LR; Edelweiss, MI; Pohlmann, PR; Stein, AT; Rosa, DD (22 November 2016). "Adjuvant platinum-based chemotherapy for early stage cervical cancer.". The Cochrane database of systematic reviews. 11: CD005342. PMID 27873308.
  3. ↑ 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.
  4. ↑ 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 38793Freely accessible. PMID 8755522.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ Johnstone, Timothy C.; Suntharalingam, Kogularamanan; Lippard, Stephen J. (2016). "The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs". Chemical Reviews. 116 (5): 3436–3486. doi:10.1021/acs.chemrev.5b00597. ISSN 0009-2665.
  8. ↑ Kelland, L. (2007). "The resurgence of platinum-based cancer chemotherapy". Nature Reviews Cancer. 7 (8): 573–584. doi:10.1038/nrc2167. PMID 17625587.
  9. ↑ 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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