Mechanisms of resistance to camptothecins

Ann N Y Acad Sci. 2000;922:46-55. doi: 10.1111/j.1749-6632.2000.tb07024.x.


Camptothecins are broad-spectrum anticancer drugs that specifically target DNA topoisomerase I. Although the availability of camptothecins has had a significant impact on cancer therapeutics, de novo or acquired clinical resistance to camptothecins is common. Studies of camptothecin resistance using yeast and mammalian cell culture models suggest three general mechanisms of resistance: (1) reduced cellular accumulation of camptothecins, (2) alteration in the structure or location of topoisomerase I, and (3) alterations in the cellular response to camptothecin-DNA-ternary complex formation. The relevance of these mechanisms to clinical drug resistance is not yet known, but evaluation of these models in clinical specimens should enhance the use of camptothecins both as single agents and in combination with other anticancer drugs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacokinetics
  • Camptothecin / pharmacology*
  • DNA Topoisomerases, Type I / metabolism
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Topoisomerase I Inhibitors


  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Topoisomerase I Inhibitors
  • DNA Topoisomerases, Type I
  • Camptothecin