Chemogenomics of Sensitivity and Resistance to Anticancer Drugs

Zunyan      Dai; Wolfgang      Sadee; Paul      Blower

Abstract

Chemogenomics integrates genomic datasets with biological and chemical characteristics of compounds. It uses genomic or proteomic profiling combined with chemoinformatics and statistics to study the response of a biological system to chemical compounds. This large-scale approach is particularly suitable for addressing chemotherapeutic resistance, a main obstacle to successful treatment of cancer patients. Chemogenomics as a discipline has been molded by a suite of datasets derived from a panel of 60 cancer cell lines that are used for drug discovery by the National Cancer Institute (NCI-60). Offering cytotoxic potencies for > 50,000 compounds across the NCI-60, and mRNA profiles, proteomes, mutations, and epigenetic factors, this unparalleled public resource enables rapid discovery of molecular targets and mechanisms of chemosensitivity/resistance. While chemogenomics holds much promise, broader impact in all fields of biology and medicine requires expansion of curated and accessible datasets of diverse biological systems, biological and chemical properties of compound libraries, and novel informatics tools for extracting the valuable information embedded in high-dimensional data. Exploiting the effects of diverse chemical probes, chemogenomics adds an important dimension to systems biology for understanding cellular functions.

Keywords: NCI-60 cell lines, dihydropyrimidine dehydrogenase (DPYD), mRNA expression, asparagine synthetase (ASNS), MetNet3D, acute myelogenous leukemia

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