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Platinum-Based Drugs in Cancer Therapy pp 149–167Cite as

How Does Cisplatin Kill Cells?

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Cisplatin is widely used as a chemotherapeutic agent. The molecular details of how it causes cells to die are largely unknown, but it is clear that its effectiveness varies quite markedly in different tumor types. Some tumors such as seminoma are highly sensitive, whereas others, such as pancreatic carcinoma, are nearly completely resistant to tolerated doses. A variety of other tumor types, of which ovarian cancer serves as a good example, are typically responsive initially but acquire resistance during the course of therapy. Some insight into the mechanisms by which cisplatin kills cells has been obtained through the identification of factors that control sensitivity to this drug and its close analog carboplatin. Five biochemical alterations have been identified that can cause cisplatin resistance in specific model systems. These include: (1) decreased cellular accumulation of cisplatin; (2) increased levels of glutathione or of glutathione-S-transferase activity; (3) increased levels of intracellular metallothioneins; (4) enhanced DNA repair; and (5) loss of DNA mismatch repair (MMR) activity (1-5). However, it is likely that several of these mechanisms operate together in most resistant cells, and at present the dominant mechanism accounting for either de novo or clinically acquired resistance is unknown. It is not even clear that there is a single dominant mechanism even within a single tumor type.

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Authors
  1. Daniel Fink
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  2. Stephen B. Howell
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Editors and Affiliations

  1. CRC Centre for Cancer Therapeutics, The Institute of Cancer Research, UK

    Lloyd R. Kelland

  2. Department of Chemistry, Virginia Commonwealth University, USA

    Nicholas P. Farrell

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© 2000 Springer Science+Business Media New York

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Fink, D., Howell, S.B. (2000). How Does Cisplatin Kill Cells?. In: Kelland, L.R., Farrell, N.P. (eds) Platinum-Based Drugs in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-012-4_7

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  • DOI: https://doi.org/10.1007/978-1-59259-012-4_7

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-091-5

  • Online ISBN: 978-1-59259-012-4

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