PMID: 9000804Dec 1, 1996Paper

Molecular basis of cis-diamminedichloroplatinum(II) resistance: a review

Journal of the Formosan Medical Association = Taiwan Yi Zhi
C C Chao

Abstract

Cisplatin is one of the most widely used chemotherapeutic agents. However, at sublethal concentrations, resistance of cells to the drug occasionally arise, which greatly limits its effectiveness in cancer therapy. In this review, the mechanisms of acquired resistance to cisplatin are elucidated. Numerous mechanisms potentially contributing to clinical cisplatin resistance have been identified, including changes in membrane permeability, detoxification pathways and the ability to remove cytotoxic lesions from DNA. Changes triggered by cisplatin selection in the resistant phenotype involve a secondary layer of complexity that may include alterations in: 1) oncogene and protein kinase signal transduction pathways: 2) growth factor and hormone responsiveness; 3) chromosome structure and gene expression; 4) ion transport; 5) thymidilate metabolism; and 6) nutrient transport and utilization. It is likely that all of these changes are part of an interconnected, multifarious response to cisplatin selection. Which of these biochemical changes come to predominate may depend on the type of cell and, particularly, on the selection procedure. In general, chronic, long-term exposure to increasing concentrations of cisplatin seems to lead to ...Continue Reading

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