Genome-wide cDNA Microarray Screening to Correlate Gene Expression Profiles with Sensitivity of 85 Human Cancer Xenografts to Anticancer Drugs

Abstract

One of the most critical issues to be solved in regard to cancer chemotherapy is the need to establish a method for predicting efficacy or toxicity of anticancer drugs for individual patients. To identify genes that might be associated with chemosensitivity, we used a cDNA microarray representing 23,040 genes to analyze expression profiles in a panel of 85 cancer xenografts derived from nine human organs. The xenografts, implanted into nude mice, were examined for sensitivity to nine anticancer drugs (5-fluorouracil, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride, adriamycin, cyclophosphamide, cisplatin, mitomycin C, methotrexate, vincristine, and vinblastine). Comparison of the gene expression profiles of the tumors with sensitivities to each drug identified 1,578 genes whose expression levels correlated significantly with chemosensitivity; 333 of those genes showed significant correlation with two or more drugs, and 32 correlated with six or seven drugs. These data should contribute useful information for identifying predictive markers for drug sensitivity that may eventually provide “personalized chemotherapy” for individual patients, as well as for development of novel drugs to overcome acquired resistance of tumor cells to chemical agents.