The present invention describes methods for selecting candidate compounds for evaluation for the treatment of cancer by defining the karyotypic complexity and heterogeneity in human cancer cells based on three components of genomic anatomy: ploidy, numerical chromosome changes, and structural chromosome rearrangements. Measures of complexity include the number of chromosomal rearrangements present in a cell line (structural complexity, SC ) and the number of chromosome deviations from the ploidy level (numerical complexity, NC). Measures of cell-to-cell chromosomal variability, which reflect the degree of ongoing instability, include numerical heterogeneity (NH) and structural heterogeneity (SH). Utilizing the methods claimed in the this application, a number of chemical compounds were identified and later determined to have increased cytotoxicity toward cancer cell lines with a specific karyotypic complexity.

The positive correlations between drug sensitivity and karyotypic complexity and heterogeneity found in this analysis (122 statistically significant positive correlations) provide a distinct opportunity to identify agents that are more active against karyotypically complex and chromosomally unstable cancer cells. Such cells would typically be found in the epithelial cancers, which cause so much therapeutic concern and frustration.