Karyotypic "state" as a potential determinant for anticancer drug discovery

Anna V. Roschke, Samir Lababidi, Giovanni Tonon, Kristen S. Gehlhaus, Kimberly Bussey, John N. Weinstein, Ilan R. Kirsch

Research output: Contribution to journalArticle

Abstract

Cancer is a genetic disease caused by genomic instability. In many cancers, this instability is manifested by chromosomal reconfigurations and karyotypic complexity. These features are particular hallmarks of the epithelial cancers that are some of the malignancies most resistant to long term control by current chemotherapeutic agents. We have asked whether we could use karyotypic complexity and instability as determinants for the screening of potential anticancer compounds. Using a panel of well characterized cancer cell lines, we have been able to identify specific groups of chemical compounds that are more cytotoxic toward the relatively more karyotypically complex and unstable panel members. Thus, we delineate an approach for the identification of "lead compounds" for anticancer drug discovery complementary to those that are focused at the outset on a given gene or pathway.

Original languageEnglish
Pages (from-to)2964-2969
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number8
DOIs
Publication statusPublished - Feb 22 2005

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Keywords

  • Cancer
  • Chromosome
  • Karyotypic complexity
  • NCI-60

ASJC Scopus subject areas

  • Genetics
  • General

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