Gene Expression Analyses for Tailoring and Optimizing Drug Treatment

GENE EXPRESSION ANALYSES FOR TAILORING AND OPTIMIZING DRUG TREATMENT 

Examples of specialized molecular therapeutics that have been developed from discoveries made using expression profiling experiments include chimeric human/murine antibodies for the treatment of various cancers. Ritux-imab (Rituxan Genentech Inc. South San Francisco, CA), an anti-CD20 antibody in use since 1997, was the first chimeric monoclonal antibody to 

A key clinical classification of breast cancer tumors is estrogen receptor (ER) expression. The more ERs are present on tumor cells, the more likely an anti-estrogen therapy such as tamoxifen can be successfully applied. Classification of each tumor is important, as only about 60%) of breast cancers are ER-positive. Initial studies set out to demonstrate that breast cancers with distinct pathological features could be separated by microarrays. Several groups demonstrated that supervised data analysis could be used to distinguish ER-positive from ER-negative tumors (74—76). 

If accurate determination of chemosensitivity were predictable by gene expression analysis, the overall number of patients receiving cytotoxic treatment unnecessarily would decrease, and the overall survival benefit derived per patient treated would increase accordingly. Large increases in the absolute survival of patients diagnosed with breast cancer, however, will require the development of novel therapeutic agents. 

Microarray-based gene expression profiling for gene and pathway discovery, functional classification of genes, and new tumor sub-classifications have also been applied to various other malignancies including lung, bladder and prostate cancer, and cutaneous melanoma (reviewed in Refs. 77 80). 

---