Targeting cancer cells by exploiting karyotypic complexity and chromosomal instability.
Multiple karyotypic abnormalities and chromosomal instability are particular hallmarks of many cancers that are relatively resistant to long term control by current chemotherapeutic agents. We have asked whether these same hallmarks, karyotypic complexity and instability, can be used 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 approaches that are focused at the outset on a given gene or pathway.
Roschke
Anna V
AV
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kirsch
Ilan R
IR
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D043171:Chromosomal Instability / Q000235:genetics; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm