Identification of compounds with preferential inhibitory activity against low-Nm23-expressing human breast carcinoma and melanoma cell lines.
We have used the COMPARE computer algorithm and Nm23 expression as a marker of tumor metastatic potential to examine the in vitro antiproliferative activity of chemotherapeutic drugs on human breast carcinoma and melanoma cell lines. None of 171 compounds in clinical use or under development and only 40 of 30,000 repository compounds exhibited preferential growth inhibition of low-Nm23-expressing, metastatically aggressive cell lines with a Pearson correlation coefficient of < or = -0.64. Characterization of one compound, NSC 645306, is presented including in vivo activity in a hollow fiber assay. The data demonstrate a novel approach to drug identification for aggressive human tumors.
Freije
J M
JM
Women's Cancers Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Lawrence
J A
JA
Hollingshead
M G
MG
De la Rosa
A
A
Narayanan
V
V
Grever
M
M
Sausville
E A
EA
Paull
K
K
Steeg
P S
PS
D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009701:Nucleoside-Diphosphate Kinase; D014157:Transcription Factors / Q000032:analysis*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins