Unstable Methotrexate Resistance in Human Small-Cell Carcinoma Associated with Double Minute Chromosomes

Gregory A. Curt, Desmond N. Carney, Kenneth H. Cowan, Jacques Jolivet, Brenda D. Bailey, James C. Drake, Chien Song Kao-Shan, John D. Minna, Bruce A. Chabner

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

Resistance to antineoplastic drugs may develop through a variety of mechanisms, including deletion of membrane-transport mechanisms, an increase in target-enzyme concentration, or a deletion of an essential drug-activating enzyme. One unique mechanism for mutation to drug resistance is amplification of the gene coding for a target protein, leading to elevated levels of the protein. In studies of cultured experimental tumor-cell lines, resistance to a variety of toxic substances, including cadmium1 and the antineoplastic drugs N-phosphonacetyl-L-aspartate2 and methotrexate,3 has been ascribed to gene amplification. The process of gene amplification in methotrexate-resistant mammalian cells may occur within a single chromosome, producing an.

Original languageEnglish (US)
Pages (from-to)199-202
Number of pages4
JournalNew England Journal of Medicine
Volume308
Issue number4
DOIs
StatePublished - Jan 27 1983
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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