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¹ Science Applications International Corp., National Cancer Institute; ² Developmental Therapeutics Program, Screening Technologies Branch, National Cancer Institute at Frederick, Frederick, Maryland; and ³ Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Ilan R. Kirsch, Amgen, 1201 Amgen Court West, AW1-J 4144, Seattle, WA 98119-3105. Phone: 206-265-7316; Fax: 206-216-5930. E-mail: lkirsch{at}amgen.com

The karyotypic features of cancer cells have not been a particular focus of anticancer drug targeting either as guidance for treatment or as specific drug targets themselves. Cancer cell lines typically have considerable, characteristic, and variable chromosomal aberrations. Here, we consider small-molecule screening data across the National Cancer Institute's 60 tumor cell line drug screening panel (NCI-60) analyzed for specific association with karyotypic variables (numerical and structural complexity and heterogeneity) determined for these same cell lines. This analysis is carried out with the aid of a self-organizing map allowing for a simultaneous assessment of all screened compounds, revealing an association between karyotypic variables and a unique part of the cytotoxic response space. Thirteen groups of compounds based on related specific chemical structural motifs are identified as possible leads for anticancer drug discovery. These compounds form distinct groups of molecules associated with relatively unexplored regions of the NCI-60 self-organizing map where anticancer agents currently standard in the clinic are not present. We suggest that compounds identified in this study may represent new classes of potential anticancer agents.

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⁴ Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org).

Received 7/ 5/05; accepted 8/10/05.