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Karyotypic "state" as a potential determinant for anticancer drug discovery
Roschke AV, Lababidi S, Tonon G, Gehlhaus KS, Bussey K, Weinstein JN, Kirsch IR.
Proc Natl Acad Sci U S A. 2005 Feb 9; [Epub ahead of print]
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.
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