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Researcher Emphasizes Opportunities for Drug Target Discovery Based on Cancer Heterogeneity at AACR

By Andrea Anderson

CHICAGO (GenomeWeb News) – There may be ways to exploit the extensive heterogeneity being uncovered through genome sequencing and other studies of cancer as a means for coming up with new treatment targets and identifying promising drug candidates, according to one presenter at this year's American Association for Cancer Research annual meeting.

Speaking as part of a session on integrative functional genomics here yesterday, University of Texas Southwestern oncology researcher Michael White said that he and his team are looking for ways to "embrace this heterogeneity" in cancer.

To do this, he explained, they have embarked on an effort to do large-scale genetic and chemical perturbations done in parallel on more than 100 cancer cell lines as a means of finding drug leads or targets.

Over the past few years they have been working to characterize and group 108 human non-small cell lung cancer cell lines based on their response profiles following exposure to hundreds of thousands of compounds and to a large set of small interfering RNAs targeting around 20,000 genes across the genome.

The team has also started folding in gene expression profiles for cell lines exposed to large sets of microRNAs, chemicals, and siRNAs targeting genes from specific pathways to get an even higher-resolution view of NSCLC lines.

By bringing these different types of high-throughput data together, White explained, researchers are beginning to uncover clusters of cell lines showing sensitivity to new compounds, along with gene mutations that correspond to response to certain compounds.

"Broad-scale parallel testing of genetic and chemical perturbations, together with high-resolution genomic characterization, is being used to parse this panel into subtypes with shared target opportunities and molecular correlates that predict response to target intervention," White and his co-authors wrote in the abstract for the presentation.

"In this way, we have begun to identify somatic allele combinations that drive sensitivity to selective gene depletions and to synthetic small molecules that target these genes and/or the biological processes they serve."

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